KR101940042B1 - A composition comprising an extract of Salvia pleia, and red ginseng, as an active ingredient for preventing or treating respiratory inflammation disease - Google Patents

A composition comprising an extract of Salvia pleia, and red ginseng, as an active ingredient for preventing or treating respiratory inflammation disease Download PDF

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KR101940042B1
KR101940042B1 KR1020170058865A KR20170058865A KR101940042B1 KR 101940042 B1 KR101940042 B1 KR 101940042B1 KR 1020170058865 A KR1020170058865 A KR 1020170058865A KR 20170058865 A KR20170058865 A KR 20170058865A KR 101940042 B1 KR101940042 B1 KR 101940042B1
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ginseng
extract
panax
confirmed
inflammatory
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KR20180124410A (en
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신한재
김효근
이문용
곽효민
민혜정
김영신
한창균
경종수
인교
김종한
김성원
장경화
김승형
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주식회사 케이티앤지
주식회사 한국인삼공사
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Priority to KR1020170058865A priority Critical patent/KR101940042B1/en
Priority to PCT/KR2018/005361 priority patent/WO2018208094A2/en
Priority to US16/611,836 priority patent/US11510955B2/en
Priority to CN201880029176.6A priority patent/CN110621326B/en
Priority to CN202111448135.0A priority patent/CN114099568B/en
Priority to JP2019562656A priority patent/JP7260233B2/en
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Abstract

본 발명은 곰보배추 및 홍삼으로 구성된 조합 추출물을 유효성분으로 함유하는 호흡기염증 질환의 예방 및 치료용 조성물에 관한 것이다. 본 발명에 따른 조합 추출물을 대상으로 활성산소종 발생 억제 평가 시험( 실험예 1)을 통하여 강력한 활성산소종 억제 효과를 나타냄을 확인하였으며, 류코트리엔(leukotriene) 발생 억제능 평가( 실험예 2) 을 통하여 강력한 류코트리엔(leukotriene) 발생 억제 효과를 나타냄을 확인하였으며, 총 기관지폐포세척액 ( BAL ; bronchoalveolar lavage ) 세포수 측정실험 (실험예 3)을 통하여 강력한 총 BAL 세포수 감소 효과를 나타냄을 확인하였으며, 기관지폐포세척액(BAL fluid)내 백혈구( leukotcyte ) 중 CD11b +/ Gr -1+ 세포비율 측정( 실험예 4) 을 통하여 강력한 CD11b+/Gr-1+ leukocyte의 비율 억제 효과를 나타냄을 확인하였으며, 폐내 시토킨 ( cytokine ) mRNA 발현 수준에 미치는 영향실험 ( 실험예 5)을 통하여 강력한 염증성 사이토카인 및 염증인자 발현 수준 억제 효과를 나타냄을 확인하였으며,기관지폐포세척액 ( BAL fluid)내 염증인자 발현 수준에 미치는 영향실험 ( 실험예 6)을 통하여 강력한 염증성 사이토카인 및 염증인자 발현 수준 억제 효과를 나타냄을 확인하였으며, 폐조직 변화에 미치는 영향실험 (실험 예 7)을 통하여 폐세포 벽이 얇아지고 교원섬유가 감소하는 것을 확인하였으며, 특히, 본원 발명의 조합 추출물을 투여시에 상승적인 기관지염증 억제 또는 치료효과를 나타냄을 확인함으로서 안전하면서 호흡기염증 질환에 대한 강력한 치료효능을 확인함으로서 호흡기염증 질환의 예방 또는 치료에 유용하게 사용될 수 있다. The present invention relates to a composition for the prevention and treatment of respiratory inflammatory diseases, which comprises a combination extract comprising pale green cabbage and red ginseng as an active ingredient. Inhibiting the active oxygen species generated by the target combined extracts according to the invention Test (Test Example 1) a strong active oxygen inhibitory effect was confirmed indicates via, leukotrienes (leukotriene) generated inhibitory ability evaluation (Test Example 2) through was confirmed strong leukotrienes (leukotriene) generated indicates an inhibitory effect, a total of BAL fluid (BAL the ; bronchoalveolar lavage) cell count measurement experiment (Experiment 3) was confirmed strong BAL total cell number refers to reduction through the bronchial lavage fluid (BAL fluid) within the white blood cells (leukotcyte) of the CD11b + / Gr -1+ cell ratio measurement ( experiment 4) the strong CD11b + / Gr-1 + rate of leukocyte inhibition effect was confirmed by the indicated, intrapulmonary Cytokine (cytokine) effects on mRNA expression level experiment (Experiment 5) was confirmed by a strong inflammatory cytokines and inflammatory markers represent the level of expression inhibitory effect, bronchoalveolar lavage (BAL fluid) Effect on experimental inflammatory factor level of expression (Example 6) has confirmed that the strong inflammatory cytokines and inflammatory markers represent the expression level of inhibitory effect through, through the effect experiments on lung tissue changes (Example 7) The closed-cell wall thinning was confirmed that the decrease in collagen fibers, In particular, by confirming that synergistic bronchial inflammation is suppressed or therapeutic effect upon administration of the combination extract of the present invention, it can be safely used for the prevention or treatment of respiratory inflammatory diseases by confirming the powerful therapeutic effect on respiratory inflammatory diseases .

Description

곰보배추 및 홍삼으로 구성된 조합 추출물을 유효성분으로 함유하는 호흡기염증 질환의 예방 및 치료용 조성물 {A composition comprising an extract of Salvia pleia, and red ginseng, as an active ingredient for preventing or treating respiratory inflammation disease}Technical Field [0001] The present invention relates to a composition for preventing and treating respiratory inflammatory diseases, which comprises a combination extract of green cabbage and red ginseng as an active ingredient,

본 발명은 곰보배추 및 홍삼으로 구성된 조합 추출물을 유효성분으로 함유하는 호흡기염증 질환의 예방 및 치료용 조성물에 관한 것이다.The present invention relates to a composition for the prevention and treatment of respiratory inflammatory diseases, which comprises a combination extract comprising pale green cabbage and red ginseng as an active ingredient.

[문헌 1] Adelroth E. How to measure airway inflammation: bronchoalveolar lavage and airway biopsies.Can Respir J. 1998:18A-21A. Review[1] Adelroth E. How to measure airway inflammation: bronchoalveolar lavage and airway biopsies. Can Respir J. 1998: 18A-21A. Review

[문헌 2] Beutner EH. IMMUNOFLUORESCENT STAINING: THE FLUORESCENT ANTIBODY METHOD. Bacteriological Reviews. 1961;25(1):49-76[Document 2] Beutner EH. IMMUNOFLUORESCENT STAINING: THE FLUORESCENT ANTIBODY METHOD. Bacteriological Reviews. 1961; 25 (1): 49-76

[문헌 3] Brandt EB, Kovacic MB, Lee GB, et al. Diesel exhaust particle induction of IL17A contributes to severe asthma. The Journal of allergy and clinical immunology. 2013;132(5)[Literature 3] Brandt EB, Kovacic MB, Lee GB, et al. Diesel exhaust particle induction of IL17A contributes to severe asthma. The Journal of Allergy and Clinical Immunology. 2013 132 (5)

[문헌 4] Minoguchi K and Adachi M. Pathophysiology of asthma. In: Cherniack NS, Altose MD, Homma I, editors. Rehabilitation of the patient with respiratory disease. New York: McGraw-Hill, 1999, pp97-104.[4] Minoguchi K and Adachi M. Pathophysiology of asthma. In: Cherniack NS, Altose MD, Homma I, editors. Rehabilitation of the patient with respiratory disease. New York: McGraw-Hill, 1999, pp 97-104.

[문헌 5] Maggi E., Immunotechnology, 3, pp233-244, 1998; Pawankar R., Curr. Opin. Allergy Clin. Immunol., 1, pp3-6, 2001;[Literature 5] Maggi E., Immunotechnology, 3, pp. 233-244, 1998; Pawankar R., Curr. Opin. Allergy Clin. Immunol., 1, pp3-6, 2001;

[문헌 6] Nandedkar SD, Feroah TR, Hutchins W, et al. Histopathology of experimentally induced asthma in a murine model of sickle cell disease. Blood. 2008;112(6):2529-2538[Literature 6] Nandedkar SD, Feroah TR, Hutchins W, et al. Histopathology of experimentally induced asthma in a murine model of sickle cell disease. Blood. 2008; 112 (6): 2529-2538

[문헌 7] Hele DJ, Belvisi MG. 2003. Novel therapies for the treatment of inflammatory airway diseases. Expert Opin Investig Drugs 12: 5-18; [Literature 7] Hele DJ, Belvisi MG. 2003. Novel therapies for the treatment of inflammatory airway diseases. Expert Opin Investig Drugs 12: 5-18;

[문헌 8] Fox JC, Fitzgerald MF. 2009. The role of animal models in the pharmacological evaluation of emerging anti-inflammatory agents for the treatment of COPD. Curr Opin Pharmacol. 9: 231-242[Document 8] Fox JC, Fitzgerald MF. 2009. The role of animal models in the pharmacological evaluation of emerging anti-inflammatory agents for the treatment of COPD. Curr Opin Pharmacol. 9: 231-242

[문헌 9] Barnes PJ. 2000. Mechanisms in COPD: differences from asthma. Chest 117: 10S-14S; [Literature 9] Barnes PJ. 2000. Mechanisms in COPD: differences from asthma. Chest 117: 10S-14S;

[문헌 10] Seatta M, Turato G, Maestrelli P, Mapp CE, Fabbri LM. 2001. Cellular and structural base of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 163: 1304-1309)[Document 10] Seatta M, Turato G, Maestrelli P, Mapp CE, Fabbri LM. 2001. Cellular and structural basis of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 163: 1304-1309)

[문헌 11] 정보섭외, 도해향약대사전, 영림사, p862-863, 1998년[Literature 11] Information Sources, Illustrated Dictionary of Contemporary Art, Yeonglim Publishing House, p 862-863, 1998

[문헌 12] 한국 공개특허 10-2013-0129868호[Document 12] Korean Patent Publication No. 10-2013-0129868

[문헌 13] 한국공개특허 10-2015-0026579호[Patent Document 13] Korean Patent Publication No. 10-2015-0026579

[문헌 14] 고려삼의 이해, 고려인삼학회, p 9, 1995[Literature 14] Understanding of Korean ginseng, Korean Ginseng Society, p 9, 1995

[문헌 15] 한국공개특허 10-2016-0021037호[Patent Document 15] Korean Patent Publication No. 10-2016-0021037

[문헌 16] 한국공개특허 10-2016-0021038호[Patent Document 16] Korean Patent Publication No. 10-2016-0021038

[문헌 17] Green LC, Wanger DA, Glogowski J, Skipper PL, Wishnok JS, and Tannenbaum SR, 1982 Analysis of nitrate, nitrite and[15N] nitrate in biologic fluids. Anual . Biochem 126: 131; [17] Green LC, Wanger DA, Glogowski J, Skipper PL, Wishnok JS, and Tannenbaum SR 1982 Analysis of nitrate, nitrite and [15N] nitrate in biologic fluids. Anual . Biochem 126: 131;

[문헌 18] Arch Pharm Res., 2003, 3,232-236).[Document 18] Arch Pharm Res ., 2003, 3, 232-236).

본 발명은 곰보배추 및 홍삼으로 구성된 조합 추출물을 유효성분으로 함유하는 호흡기염증 질환의 예방 및 치료용 조성물에 관한 것이다.The present invention relates to a composition for the prevention and treatment of respiratory inflammatory diseases, which comprises a combination extract comprising pale green cabbage and red ginseng as an active ingredient.

일반적으로 염증 반응은 생체의 세포나 조직에 어떠한 기질적 변화를 가져오는 침습이 가해질 때 그 손상부위를 수복 재생하려고 하는 생체의 방어 반응과정이다. 따라서 이러한 일련의 반응에는 국소의 혈관, 체액의 각종 조직세포, 면역관여 세포 등이 포함된다. 최근 분자생물학의 발달과 더불어 염증성 질환이 사이토카인(cytokine)이라는 분자 수준에서의 이해가 시도되고 있으며, 이러한 질환에 영향을 주는 인자들도 하나씩 규명되고 있다.In general, an inflammatory reaction is a defensive reaction process of a living body that attempts to repair and regenerate a damaged region when an invasion of biological changes occurs in the cell or tissue of the living body. Thus, these series of reactions include localized blood vessels, various tissue cells of body fluids, and immune-mediated cells. With the recent development of molecular biology, inflammatory diseases have been attempted to be understood at the molecular level of cytokine, and factors affecting these diseases are also being clarified one by one.

알러지 반응은 그 반응 형태에 의해 I형, II형, III형 및 IV형의 4 가지 유형으로 분류될 수 있고, 또는 항원에 의한 재감작(感作) 후 발증까지의 시간에 의해서 I형, II형 및 III형 알러지는 즉시형 알러지라고 불리며, IV형 알러지는 지연형 알러지로 분류될 수 있다. Allergic reactions can be classified into four types according to the type of reaction: type I, type II, type III, and type IV, or type I, type II according to the time until onset after re- Type III and Type III allergies are called immediate allergies, and Type IV allergies can be classified as delayed allergies.

이 중, I형 알러지는 IgE 항체가 관여하는 반응으로서, 아나필락시형 알러지라고 불리우며, 여기에는 기관지 천식, 아토피성 질환(피부염, 장염 등), 화분증 등의 알러지성 비염, 알러지성 결막염, 음식물 알러지 등이 포함된다.Among them, type I allergy is a reaction involving IgE antibody, which is called anaphylactic type allergy, and includes allergic rhinitis such as bronchial asthma, atopic diseases (dermatitis, enteritis), hay fever, allergic conjunctivitis, .

천식(asthma)이란 여러 가지 자극에 대한 기도의 과민성을 그 특징으로 하는 질환으로 기도의 광범위한 협착에 의해 발생하는 천명(喘鳴), 호흡곤란, 기침 등의 임상 증세들은 자연히 혹은 치료에 의해 가역적으로 호전될 수 있다. 대부분의 천식은 알러지성이며, 만성 기도염증(chronic airway inflammation)과 기도 과민반응성(bronchial hyperresponsiveness)이 특징이다(Minoguchi K and Adachi M. Pathophysiology of asthma. In: Cherniack NS, Altose MD, Homma I, editors. Rehabilitation of the patient with respiratory disease. New York: McGraw-Hill, 1999, pp97-104).Asthma is a disorder characterized by airway hyperresponsiveness to various stimuli. Clinical symptoms such as wheezing, dyspnea, and cough caused by extensive stenosis of the airways can be reversed naturally or by treatment. . Most asthma is allergic and is characterized by chronic airway inflammation and bronchial hyperresponsiveness (Minoguchi K and Adachi M. Pathophysiology of asthma. In: Cherniack NS, Altose MD, Homma I, editors New York: McGraw-Hill, 1999, pp 97-104).

천식은 그 원인에 따라 외인성 천식과 내인성 천식으로 나누어질 수 있다. 외인성 천식의 경우 원인 항원에 노출되었을 때 증상이 나타나는 천식을 말한다. 원인 항원에 대한 피부시험이나 기관지 유발시험이 양성반응을 보이며 발병 연령이 어린 것이 일반적이다. 집 먼지, 진드기가 가장 많은 원인 항원이며, 그밖에 꽃가루, 동물의 상피, 곰팡이 등이 원인 항원으로 작용한다. 내인성 천식의 경우에는 상기도 감염, 운동, 정서불안, 한랭 기후 및 습도의 변화 등이 천식을 유발하거나 악화시키는 경우인데, 성인형 천식에서 흔히 볼 수 있다. 그 외에도 약물에 의해 유발되는 천식, 운동 유발성 천식 및 직업성 천식 등이 있다.Asthma can be divided into extrinsic asthma and endogenous asthma depending on its cause. In the case of exogenous asthma, it refers to asthma that causes symptoms when exposed to a causative antigen. Skin test or bronchial induction test for the causative antigen is positive and it is common that the onset age is young. House dust, and ticks are the major causative antigens, and pollen, animal epithelium, and fungi also act as causative antigens. In the case of endogenous asthma, upper respiratory infections, exercise, emotional disturbances, changes in cold weather and humidity cause or exacerbate asthma, which is common in adult asthma. Other medications include asthma, exercise-induced asthma, and occupational asthma.

천식은 TH2(T helper 2) 타입 면역세포가 생성하는 인터루킨-4, 5, 13에 의해 염증세포가 증식, 분화 및 활성화되어 기도 및 기도 주변 조직으로 이동, 침윤하기 때문에 만성 염증질환으로도 인식되고 있다(Elias JA, et al., J. Clin. Invest., 111, pp291-297, 2003). 천식을 앓고 있는 환자의 기관지에서 활성화된 호산구, 비만세포, 폐포 대식세포 등의 염증세포는 다양한 염증매개인자들(시스테인 류코트리엔, 프로스타글란딘 등)을 분비하면서 강력한 기관지 수축작용에 관여한다(Maggi E., Immunotechnology, 3, pp233-244, 1998; Pawankar R., Curr. Opin. Allergy Clin. Immunol., 1, pp3-6, 2001; Barnes PJ, et al., Pharmacol Rev., 50, pp515-596, 1998).Asthma is also recognized as a chronic inflammatory disease because inflammatory cells are proliferated, differentiated and activated by IL-4, 5, and 13 produced by TH2 (T helper 2) type immune cells, (Elias JA, et al., J. Clin. Invest., 111, pp. 291-297, 2003). Inflammatory cells such as eosinophils, mast cells, and alveolar macrophages that are activated in the bronchi of patients suffering from asthma are involved in strong bronchoconstriction by secretion of various inflammatory mediators (cysteine leukotrienes, prostaglandins, etc.) (Maggi E., Barnes PJ, et al., Pharmacol. Rev., 50, pp. 515-596, 1998. Immunotechnology, 3, pp 233-244, 1998; Pawankar R., Curr. Opin. Allergy Clin. Immunol., 1, pp 3-6, ).

따라서 염증세포 활성화에 관여하는 IL-4, IL-5, IL-13 등 사이토카인 및 면역글로불린 E의 생산과 이들의 작용으로 호산구 등 염증세포에서 분비되는 시스테인 류코트리엔 생합성 등은 염증 및 알러지 반응과 이로 인한 천식을 유발하는 주요 원인이므로 이들의 생산을 억제하기 위한 약물을 개발하고자 많은 연구가 진행되고 있다.Therefore, the production of cytokines and immunoglobulin E such as IL-4, IL-5, and IL-13, which are involved in inflammatory cell activation, and the cysteine leukotriene biosynthesis secreted from inflammatory cells such as eosinophils, As a major cause of asthma, many studies are under way to develop drugs to suppress their production.

또한, 만성 폐쇄성 폐질환은, 가역적인 기류 폐쇄와 알러지성 기관지 염증 반응을 주된 특징으로 나타내는 천식과는 구분되어서 적합하게 치료되어야 하지만, 현재의 치료법은 단지 증상의 경감을 제공함에 불과하고, 최근 치료법 중 어느 것도 만성 폐쇄성 폐질환의 근본적인 치료 효과를 임상적인 결과로 나타내지 못하고 있다 (Hele DJ, Belvisi MG. 2003. Novel therapies for the treatment of inflammatory airway diseases. Expert Opin Investig Drugs 12: 5-18; Fox JC, Fitzgerald MF. 2009. The role of animal models in the pharmacological evaluation of emerging anti-inflammatory agents for the treatment of COPD. Curr Opin Pharmacol. 9: 231-242)In addition, chronic obstructive pulmonary disease should be appropriately treated differently from asthma, which is characterized by reversible airflow obstruction and allergic bronchial inflammatory response. However, the current treatment is merely a symptom relief, (Hele DJ, Belvisi MG, 2003. Novel therapies for the treatment of inflammatory airway diseases. Expert Opin Investig Drugs 12: 5-18; Fox JC , Fitzgerald MF. 2009. Curr Opin Pharmacol. 9: 231-242)

천식과 COPD는 원칙적으로 상이한 병리기전을 나타내는데, 예를 들어, (1) 염증세포 면에서, 천식은 비만세포(mast cell), 호산구(Eosinophils), CD4+ 세포 (Th2), 대식세포(Macrophages) 등이 주로 작용하는데 반하여, COPD는 호중구(Neutrophils), CD8+ 세포 (Tc) 등이 주로 작용한다는 점에서 상이하며; (2) 염증매개인자 면에서, 천식은 류코트리엔(Leukotriene B), 히스타민(Histamine), IL-4, IL-5, IL-13, 에오탁신(Eotaxin), RANTES, 산화적 스트레스(Oxidative stress) 등이 주로 관여되는데 반하여, COPD는 TNF-alpha, IL-8, GRO-alpha 등이 주로 관여된다는 점에서 상이하며; (3) 염증현상 면에서, 천식은 전체 기도에 작용하여, AHR(기도과민반응 과민), 상피성 쉐딩(Epithelial shedding), 섬유증(Fibrosis), 조직질실상 발전이 없으며(no parenchymal involvement), 점액분비(muscus secretion), 비교적 가역적 기류장애 현상, 기침, 재채기, 호흡곤란(dyspnea)를 주로 어린 시기에 발생하는 데 반하여, COPD는 말초 기도에 작용하여, 상피성 변성(Epithelial metaplasia), 조직질실상 손상 (parenchymal destruction), 비교적 비가역적 기류장애 현상, 만성 기관지염, 폐기종을 주로 성인기에 발생하는 점에서 상이한 점 등의 별개의 병리기전을 갖는 것으로 알려져 있다 (Barnes PJ. 2000. Mechanisms in COPD: differences from asthma. Chest 117: 10S-14S; Seatta M, Turato G, Maestrelli P, Mapp CE, Fabbri LM. 2001. Cellular and structural base of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 163: 1304-1309).Asthma and COPD, in principle, represent different pathological mechanisms. For example, (1) asthma in mast cells, mast cells, eosinophils, CD4 + cells (Th2), macrophages Whereas COPD differs in that neutrophils, CD8 + cells (Tc), etc. mainly act; (2) In terms of inflammatory mediators, asthma is associated with leukotriene B, histamine, IL-4, IL-5, IL-13, Eotaxin, RANTES, oxidative stress , Whereas COPD is different in that TNF-alpha, IL-8, and GRO-alpha are mainly involved; (3) In terms of inflammation, asthma affects the entire airway and is characterized by AHR (hypersensitive hypersensitivity), epithelial shedding, fibrosis, no parenchymal involvement, COPD acts on the peripheral airways, leading to the formation of epithelial metaplasia, histological metaplasia, dyspnea and dyspnea, while muscularis secretion, relatively reversible airflow obstruction, cough, sneezing, It is known that parenchymal destruction, relatively irreversible airflow obstruction, chronic bronchitis and emphysema are different in that they occur mainly in adulthood (Barnes PJ 2000. Mechanisms in COPD: differences Asthma, Chest 117: 10S-14S, Seatta M, Turato G, Maestrelli P, Mapp CE, Fabbri LM 2001. Cellular and structural base of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 163: 1304-1309).

곰보배추는 꿀풀과(Labiatae)에 속하는 배암차즈기(Salvia pleia R. Br.)의 전초로서, 설견초, 청와초, 마마초, 과동청, 수양이 등으로도 불리며 성분으로는 플라보노이드 (flavonoids), 호모플란타기미닌 (homoplantaginin), 히스피둘린 (hispidulin), 에우카포놀린 (eupafolin), 에우카포놀린-7-글루코시드 (eupafolin-7-glucoside) 외에도 페놀성 물질, 정유성분, 사포닌, 등의 성분이 알려져 있다 [정보섭외, 도해향약대사전, 영림사, p862-863, 1998년).It is also known as Salvia pleia R. Br., Which is a member of the Labiatae family. It is also called "Ganoderma lucidum" In addition to homoplantaginin, hispidulin, eupafolin, eupafolin-7-glucoside, phenolic substances, essential oil components, saponins, etc. The composition of the compound is known [Information Information, Illustrated Dictionary of Containing Medicine, Yeonglim Publishing House, p. 862-863, 1998).

곰보배추(Salvia plebeia R. Br.)의 추출물 또는 이의 분획물을 유효성분으로 포함하는 STAT3 매개 질환의 예방 또는 치료용 약학적 조성물(한국 공개특허 10-2013-0129868호); 곰보배추(Salvia plebeia) 등의 생약 추출물의 알러지성 또는 비알러지성 피부질환의 치료 및 예방에 유용한 조성물 (한국공개특허 10-2015-0026579호) 등의 선행문헌이 개시된 바가 있다. A pharmaceutical composition for preventing or treating STAT3 mediated diseases comprising an extract of Salvia cabbage (Salvia plebeia R. Br.) Or a fraction thereof as an active ingredient (Korean Patent Laid-Open No. 10-2013-0129868); A composition useful for the treatment and prevention of allergic or non-allergic skin diseases of herbal medicine extracts such as Salvia plebeia (Korean Patent Laid-Open No. 10-2015-0026579) has been disclosed.

인삼은 파낙스 (Panax)속에 속하는 다년생 식물로, 파낙스속 식물은 식물 분류학상 오가피과 (Araliaceae)에 속하는 다년생 숙근초로서 지구상에 십여종이 알려져 있으며, 대표적인 종으로 고려인삼 (Panax ginseng), 화기삼 (Panax quinquefolia), 전칠삼 (삼칠, Panax notoginseng), 죽절삼 (Panax vietnamensis)등이 있다. (고려삼의 이해, 고려인삼학회, p 9, 1995; Advances in Ginseng Research, 고려인삼학회, p 127, 1998) 기타 파낙스속 식물로는 파낙스 엘레가티오르 (Panax elegatior), 파낙스 완지아누스 (Panax wangianus), 파낙스 피핀라티푸스 (Panax bipinratifidus)등이 있다. Ginseng is a perennial plant belonging to the genus Panax (Panax), Panax genus plant is a dozen paper known in the earth as a perennial plant belonging to the category sukgeuncho haksang ohgapigwa (Araliaceae), ginseng (Panax ginseng) as a representative species, hwagisam (Panax quinquefolia), jeonchilsam (thirty-seven, Panax notoginseng , and Panax vietnamensis . Advances in Ginseng Research, Korean Ginseng Society, p 127, 1998). Other plants belonging to the genus Panax include Panax elegans ( Panax elegans) elegatior), Panax Wan Jia Augustine (Panax wangianus), Panax Pippin called typhus (Panax bipinratifidus) and the like.

예로부터 인삼은 피로회복이나 정력증강에 유효하다고 알려져 있다. 실제로 인삼은 탐색활동의 증가, 자발운동의 감소, 경련 역치의 상승, 기억력 증가, 진통효과 및 항혈소판작용이 있는 것으로 알려져 있으나 (고려삼의 이해, 고려인삼학회, p 9, 1995), 각각의 작용은 그다지 높지 않다.From ancient times, ginseng has been known to be effective in restoring fatigue and increasing strength. In fact, ginseng is known to have an increase in search activity, a decrease in spontaneous movement, a rise in spasticity threshold, an increase in memory, an analgesic effect and an antiplatelet effect (understanding of Korean ginseng, Korean Ginseng Association, p 9, 1995) Is not very high.

인삼에 함유된 여러 가지 성분들 가운데, 강한 약리학적 활성을 나타냄으로써 인삼의 약효를 대표할 수 있는 성분은 진세노사이드 (ginsenoside) 라고 명명된 인삼 유래 배당체 사포닌 성분이다. 특히 파낙스속 식물에는 다른 식물과는 달리 담마란 (dammarane) 골격에 1 - 4 개의 당이 결합되어 있는 사포닌을 공통으로 함유하고 있다. 이는 인삼의 이차 대사 산물로서 인삼 특이 성분이며, 그 함량은 약 3 ~ 6% 정도를 차지하는 것으로 알려져 있다. 고려인삼에 함량이 높은 사포닌은 진세노사이드 Rb1, Rb2, Rc, Rd, Rg1, Re 등이다. 이러한 사포닌 성분들은 다양한 약효를 나타내는데 그 구조에 따라 약효의 종류와 강도가 다르다 (고려삼의 이해, 고려인삼학회지, p 9, 1995).Among the various components contained in ginseng, the ginseng saponin component derived from ginseng called ginsenoside is a component that can represent the pharmacological activity of ginseng by exhibiting strong pharmacological activity. Especially in plants of the genus Panax, unlike other plants, 1 - 4 sugar - bonded saponin is common in the dammarane skeleton. It is known that ginseng is a secondary metabolite of ginseng and its content is about 3 ~ 6%. The high content of saponins in ginseng is ginsenoside binary Rb 1, Rb 2, R c , R d, Rg 1, Re and the like. These saponin components exhibit various pharmacological effects, depending on their structure, and the types and intensities of the pharmacological effects are different (understanding of Korean ginseng, Journal of Korean Ginseng , p 9, 1995).

진세노사이드는 열과 압력에 기인한 물리화학적 가공 과정에 의하여 구조적인 변화를 거치게 되며, 이렇게 생성된 새로운 진세노사이드는 보다 미량에서도 강력한 생리활성을 나타낸다. 전통적인 수치생약의 일종인 홍삼은 인삼의 특수한 증숙, 건조과정에 의해 제조되며, 홍삼 중에는 진세노사이드의 구조적 변화에 의해 생성된 인삼에서는 발견되지 않는 홍삼 특이 사포닌을 함유하고 있다. 홍삼의 약효가 인삼보다 강하다고 알려져 있는 것은 열에 의해 새롭게 생성된 홍삼특이사포닌 (red ginseng unique saponins) 에 의한 것이며, 진세노사이드 Rg2, 진세노사이드 Rg3, 진세노사이드 Rg5, 진세노사이드 Rh2, 진세노사이드 Rh3, 진세노사이드 Rh4, 진세노사이드 Rs1, 진세노사이드 Rs2, 진세노사이드 Rs3 등의 종류가 보고되었다.(Bae EA, Han MJ, Shin YW, Kim DH. 2006. Inhibitory effects of Korean red ginseng and its genuine constituents ginsenosides Rg3, Rf, and 꼬2 in mouse passive cutaneous anaphylaxis reaction and contact dermatitis models. Biol. Pharm. Bull. 29: 1862-1867)The ginsenoside undergoes a structural change by physico-chemical processing due to heat and pressure, and the new ginsenoside thus produced exhibits a strong physiological activity even at a smaller amount. Traditional red ginseng, a kind of ginseng, is produced by special cooking and drying process of ginseng. Red ginseng contains red ginseng saponin which is not found in ginseng produced by the structural change of ginsenoside. It is known that the efficacy of red ginseng is stronger than that of ginseng is due to red ginseng unique saponins newly produced by heat, and the ginsenosides Rg 2 , ginsenoside Rg 3 , ginsenoside Rg 5 , ginsenoside There have been reported types of Rh 2 , ginsenoside Rh 3 , ginsenoside Rh 4 , ginsenoside Rs 1 , ginsenoside Rs 2 , and ginsenoside Rs 3 (Bae EA, Han MJ, Shin YW, Kim DH. 2006. Inhibitory effects of Korean red ginseng and its genetic constituents Ginsenosides Rg3, Rf, and 2 in mouse passive cutaneous anaphylaxis reaction and contact dermatitis models. Biol. Pharm. Bull. 29: 1862-1867)

인삼(Panax ginseng C.A. Meyer)은 오가피나무과(Araliaceae) 인삼속에 속하는 다년생 초본류로서 한방에서는 그 뿌리를 주로 이용하고 있는 대표적인 약용작물 중의 하나이다. 수확 후 가공 방식에 따라 4-6년 재배하여 수확한 후 가공하지 않은 생삼을 수삼, 4-6년근 수삼을 껍질을 벗겨내고 그대로 햇볕에서 자연 건조하거나 60℃ 이하의 열풍으로 건조시킨 인삼을 백삼, 4-6년근 수삼을 껍질을 벗기지 않은 상태로 증기로 쪄서 건조시킨 인삼을 홍삼으로 각각 구분한다.Ginseng (Panax ginseng C.A. Meyer) is a perennial herbaceous plant belonging to the genus Ginseng (Araliaceae). It is one of the representative medicinal crops mainly used in oriental herb. After 4 to 6 years of harvesting according to the post-harvest processing method, the unprocessed raw ginseng is peeled off from fresh ginseng and 4-6 years old ginseng, dried naturally in the sun or dried by hot air at 60 ° C or less, Ginseng, steamed with steam for 4-6 years, without peel, is classified into red ginseng.

본원 발명자들은 익모초 특정 추출물을 유효성분으로 포함하는 호흡기 염증질환의 예방 또는 치료용 조성물(한국공개특허 10-2016-0021037호) 및 측백엽 특정 추출물 또는 이로부터 분리된 화합물을 유효성분으로 포함하는 호흡기 염증질환의 예방 또는 치료용 조성물 (한국공개특허 10-2016-0021038호)에 대한 발명들을 지속적으로 수행하여 왔다.The present inventors have found that a composition for preventing or treating respiratory inflammatory disease comprising an extract of motherwort as a specific active ingredient (Korean Patent Laid-Open Publication No. 10-2016-0021037) and a composition comprising a specific extract of leaves or a compound isolated therefrom as an active ingredient, (Korean Patent Laid-open No. 10-2016-0021038) have been continuously carried out.

그러나, 상기 문헌의 어디에도 곰보배추 및 홍삼으로 구성된 조합 추출물을 유효성분으로 함유하는 호흡기염증 질환에 대한 치료효과가 개시되거나 교시된 바는 없다.However, none of the above documents discloses or teaches the therapeutic effect on respiratory inflammatory diseases containing a combination extract comprising pale blue cabbage and red ginseng as an active ingredient.

이에, 본 발명자들은 호흡기염증 질환에 유효한 천연물 자원을 이용한 치료제 개발 및 새로운 조합을 탐색한 결과, 곰보배추 및 홍삼의 조합 추출물을 대상으로 활성산소종 발생 억제 평가 시험( 실험예 1)을 통하여 강력한 활성산소종 억제 효과를 나타냄을 확인하였으며, 류코트리엔 ( leukotriene ) 발생 억제능 평가(실험예 2) 을 통하여 강력한 류코트리엔(leukotriene) 발생 억제 효과를 나타냄을 확인하였으며, 총 기관지폐포세척액 ( BAL ; bronchoalveolar lavage ) 세포수 측정실험 ( 실험예 3)을 통하여 강력한 총 BAL 세포수 감소 효과를 나타냄을 확인하였으며, 기관지폐포세척액(BAL fluid)내 백혈구( leukotcyte ) 중 CD11b+/Gr-1+ 세포비율 측정( 실험예 4) 을 통하여 강력한 CD11b+/Gr-1+ leukocyte의 비율 억제 효과를 나타냄을 확인하였으며, 폐내 시토킨 ( cytokine ) mRNA 발현 수준에 미치는 영향실험 ( 실험예 5)을 통하여 강력한 염증성 사이토카인 및 염증인자 발현 수준 억제 효과를 나타냄을 확인하였으며, 기관지폐포세척액(BAL fluid)내 염증인자 발현 수준에 미치는 영향실험 ( 실험예 6)을 통하여 강력한 염증성 사이토카인 및 염증인자 발현 수준 억제 효과를 나타냄을 확인하였으며, 폐조직 변화에 미치는 영향실험 (실험 예 7)을 통하여 폐세포 벽이 얇아지고 교원섬유가 감소하는 것을 확인하였으며, 특히, 본원 발명의 조합 추출물을 투여시에 상승적인 기관지염증 억제 또는 치료효과를 나타냄을 확인함으로서 안전하면서 호흡기염증 질환에 대한 강력한 치료효능을 확인함으로서 호흡기염증 질환의 예방 또는 치료에 유용하게 사용될 수 있음을 확인하여, 본 발명을 완성하였다. Thus, the inventors of respiratory inflammatory diseases result of the search and development of new therapeutic agents combined with the natural resources available to, it blisters cabbage and active targeting a combination of ginseng extract oxygen species suppress generation evaluation tests (Example 1) a strong active oxygen inhibitory effect was confirmed indicates via, leukotrienes (leukotriene) generated inhibitory ability evaluation (Test Example 2) through was confirmed strong leukotrienes (leukotriene) generated indicates an inhibitory effect, a total of BAL fluid (BAL the ; bronchoalveolar lavage ) Cell number measurement experiment ( Experimental example 3), and a strong CD11b + / Gr ( 1/2 ) ratio was observed through the measurement of CD11b + / Gr-1 + cell ratio in leukocyte in BAL fluid ( Experimental Example 4) has confirmed that the inhibitory effect refers to the ratio of the leukocyte -1+, intrapulmonary Cytokine (cytokine) was through the effect on mRNA expression level experiment (Example 5) confirmed the strong inflammatory cytokines and inflammatory markers represent the level of expression inhibitory effect, bronchoalveolar lavage (BAL fluid) on the inflammatory factor expression levels impact test (test example 6) has confirmed that the strong inflammatory cytokines and inflammatory markers represent the expression level of inhibitory effect through, through the effect experiments on lung tissue changes (Example 7) The closed-cell wall thinning was confirmed that the decrease in collagen fibers, In particular, by confirming that synergistic bronchial inflammation is suppressed or therapeutic effect upon administration of the combination extract of the present invention, it can be safely used for the prevention or treatment of respiratory inflammatory diseases by confirming the powerful therapeutic effect on respiratory inflammatory diseases To complete the present invention.

상기의 목적을 달성하기 위한 하나의 양태로서, 본 발명은 곰보배추 및 홍삼으로 구성된 조합 추출물을 유효성분으로 함유하는 호흡기염증 질환의 예방 및 치료용 약학조성물을 제공한다.In one aspect of the present invention, there is provided a pharmaceutical composition for preventing and treating respiratory inflammatory disease, which comprises, as an active ingredient, a combination extract consisting of pale green cabbage and red ginseng.

또한, 본 발명은 곰보배추 및 홍삼으로 구성된 조합 추출물을 유효성분으로 함유하는 호흡기염증 질환의 예방 및 개선용 건강기능식품을 제공한다.The present invention also provides a health functional food for prevention and improvement of respiratory inflammatory diseases, which comprises, as an active ingredient, a combination extract composed of pungent Chinese cabbage and red ginseng.

본원에서 정의되는 곰보배추 및 홍삼으로 구성된 조합은 바람직하게는, 건조 중량 상대 배합비가 1 : 0.01 내지 100(w/w)의 배합 중량부, 바람직하게는, 1 : 0.5 내지 50(w/w)의 배합 중량부, 보다 바람직하게는, 1: 0.1 내지 10(w/w)의 배합 중량부, 보다 더 바람직하게는 1: 0.3 내지 5 (w/w)의 배합 중량부, 가장 바람직하게는 1: 1 내지 3 (w/w)의 배합 중량부인 조합을 포함한다. The combination consisting of pale green cabbage and red ginseng as defined herein preferably has a dry weight relative proportion of 1: 0.01 to 100 (w / w), preferably 1: 0.5 to 50 (w / w) More preferably 1: 0.1 to 10 (w / w), more preferably 1: 0.3 to 5 (w / w), most preferably 1: : 1 to 3 (w / w).

본원에서 정의되는 홍삼은 3 내지 8년근 고려인삼 (Panax ginseng), 화기삼 (Panax quinquefolia), 전칠삼 (삼칠, Panax notoginseng), 죽절삼 (Panax vietnamensis), 파낙스 엘레가티오르 (Panax elegatior), 파낙스 완지아누스 (Panax wangianus), 또는 파낙스 피핀라티푸스 (Panax bipinratifidus) 등의 인삼, 바람직하게는 5 내지 7년근 인삼, 바람직하게는 6년근 인삼을 10 내지 60℃, 바람직하게는 상온에서 약 1 내지 24시간, 바람직하게는 1 내지 3시간 동안, 1차로 자연건조시키는 제 1단계; 상기 자연 건조된 인삼을 세척하고 2차로 수분만 제거되도록 자연 건조시키는 제 2단계; 상기 건조된 인삼을 60 내지 120℃, 바람직하게는 80 내지 110℃에서, 약 1 내지 48시간, 바람직하게는 1 내지 12시간, 보다 바람직하게는 1 내지 3시간 동안 1차 증숙하는 제 3단계; 상기 1차 증숙된 인삼을 30 내지 80℃, 바람직하게는 40 내지 70℃에서 약 1 내지 72시간, 바람직하게는 2 내지 48시간, 보다 바람직하게는 4 내지 12시간 동안, 3차 건조시켜 수분함량 40 내지 70%, 바람직하게는, 45 내지 55% 범위의 1차 건조물을 수득하는 제 4단계; 상기 1차 건조물을 공정을 통하여 10 내지 60℃, 바람직하게는 15 내지 35℃에서 약 2일 내지 30일, 바람직하게는 6일내지 20일 동안 자연 건조시켜 수분함량 10 내지 20%, 바람직하게는, 12 내지 17% 범위의 최종 홍삼 건조물을 수득하는 제 5단계 공정을 통하여 수득된 홍삼임을 특징으로 한다.As defined herein, the red ginseng is preferably selected from the group consisting of Panax ginseng , Panax ginseng quinquefolia), jeonchilsam (thirty-seven, Panax notoginseng , Panax vietnamensis , Panax elegatior , Panax wangianus ), or Panax papine latipus ( Panax bipinratifidus ), preferably 5 to 7 years old ginseng, preferably 6-year old ginseng, at 10 to 60 ° C, preferably at room temperature for about 1 to 24 hours, preferably 1 to 3 hours, A first step of drying; A second step of washing the naturally dried ginseng and naturally drying the ginseng to remove only water in the second step; A third step of firstly agitating the dried ginseng at 60 to 120 DEG C, preferably 80 to 110 DEG C for about 1 to 48 hours, preferably 1 to 12 hours, more preferably 1 to 3 hours; The firstly mixed ginseng is tertiary-dried at 30 to 80 ° C, preferably at 40 to 70 ° C for about 1 to 72 hours, preferably for 2 to 48 hours, more preferably for 4 to 12 hours to obtain a water content A fourth step of obtaining a primary dried product in the range of 40 to 70%, preferably 45 to 55%; The primary dried product is naturally dried at a temperature of 10 to 60 캜, preferably 15 to 35 캜 for about 2 to 30 days, preferably 6 to 20 days, so that the moisture content is 10 to 20% , And 12 to 17% of the final red ginseng dried product obtained in the fifth step process.

본원에서 정의되는 추출물은 정제수를 포함한 물, 주정, 탄소수 1 내지 4의 저급알코올 또는 이들의 혼합용매, 바람직하게는 물, 또는 물 및 탄소수 1 내지 4의 저급알코올 혼합용매, 보다 바람직하게는, 물 또는 10 내지 100% (v/v) 에탄올 또는 주정, 보다 더 바람직하게는 물 또는 20 내지 80% (v/v) 에탄올 또는 주정에 가용한 추출물을 포함한다.The extracts defined herein may be prepared by mixing water, a spirit, a lower alcohol having 1 to 4 carbon atoms or a mixed solvent thereof, preferably water, or a mixture of water and a lower alcohol having 1 to 4 carbon atoms, more preferably water Or extracts soluble in 10 to 100% (v / v) ethanol or alcohol, more preferably water or 20 to 80% (v / v) ethanol or alcohol.

본 발명의 추출물을 유효성분으로 함유하는 조성물은, 조성물 총 중량에 대하여 상기 추출물을 0.1 ~ 50 중량% 포함한다. The composition containing the extract of the present invention as an active ingredient contains 0.1 to 50% by weight of the above extract relative to the total weight of the composition.

본원에서 정의되는 "호흡기염증 질환"이란 비염, 중이염, 인후염, 편도염, 폐렴, 천식 및 만성 폐쇄성 폐질환으로 이루어지는 군으로부터 선택되는 어느 하나일 수 있으며, 이에 한정되지 않는다.The term " respiratory inflammatory disease " as defined herein includes, but is not limited to, any one selected from the group consisting of rhinitis, otitis media, sore throat, tonsillitis, pneumonia, asthma and chronic obstructive pulmonary disease.

본 발명에서 사용되는 용어, "예방"은 상기 추출물을 포함하는 조성물의 투여로 염증, 알러지 또는 천식을 억제 또는 지연시키는 모든 행위를 의미한다.As used herein, the term " prophylactic " means any action that inhibits or delays inflammation, allergy or asthma by administration of a composition comprising the extract.

또한, 본 발명에서 사용되는 용어 "치료"는, 상기 추출물을 포함하는 조성물의 투여로 질환의 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미한다. The term " treatment " as used in the present invention means all the actions of improving or alleviating the symptom of the disease upon administration of the composition containing the extract.

예를 들어, 본 발명의 홍삼은 3 내지 8년근 인삼, 바람직하게는 5 내지 7년근 인삼, 바람직하게는 6년근 인삼을 10 내지 60℃, 바람직하게는 상온에서 약 1 내지 24시간, 바람직하게는 1 내지 3시간 동안, 1차로 자연건조시키는 제 1단계; 상기 자연 건조된 인삼을 세척하고 2차로 수분만 제거되도록 자연 건조시키는 제 2단계; 상기 건조된 인삼을 60 내지 120℃, 바람직하게는 80 내지 110℃에서, 약 1 내지 48시간, 바람직하게는 1 내지 12시간, 보다 바람직하게는 1 내지 3시간 동안 1차 증숙하는 제 3단계; 상기 1차 증숙된 인삼을 30 내지 80℃, 바람직하게는 40 내지 70℃에서 약 1 내지 72시간, 바람직하게는 2 내지 48시간, 보다 바람직하게는 4 내지 12시간 동안, 3차 건조시켜 수분함량 40 내지 70%, 바람직하게는, 45 내지 55% 범위의 1차 건조물을 수득하는 제 4단계; 상기 1차 건조물을 공정을 통하여 10 내지 60℃, 바람직하게는 15 내지 35℃에서 약 2일 내지 30일, 바람직하게는 6일내지 20일 동안 자연 건조시켜 수분함량 10 내지 20%, 바람직하게는, 12 내지 17% 범위의 최종 홍삼 건조물을 수득하는 제 5단계 공정을 통하여 본 발명의 홍삼 건조분말을 수득가능하다. For example, the red ginseng of the present invention can be administered to a human being at a temperature of 10 to 60 ° C, preferably at room temperature for about 1 to 24 hours, preferably about 3 to 8 years of ginseng, preferably 5 to 7 years of ginseng, A first step of firstly naturally drying for 1 to 3 hours; A second step of washing the naturally dried ginseng and naturally drying the ginseng to remove only water in the second step; A third step of firstly agitating the dried ginseng at 60 to 120 DEG C, preferably 80 to 110 DEG C for about 1 to 48 hours, preferably 1 to 12 hours, more preferably 1 to 3 hours; The firstly mixed ginseng is tertiary-dried at 30 to 80 ° C, preferably at 40 to 70 ° C for about 1 to 72 hours, preferably for 2 to 48 hours, more preferably for 4 to 12 hours to obtain a water content A fourth step of obtaining a primary dried product in the range of 40 to 70%, preferably 45 to 55%; The primary dried product is naturally dried at a temperature of 10 to 60 캜, preferably 15 to 35 캜 for about 2 to 30 days, preferably 6 to 20 days, so that the moisture content is 10 to 20% , And 12 to 17% by weight of the dried red ginseng powder of the present invention.

또한 본 발명의 조합 추출물은 하기와 같이 제조될 수 있다. The combination extract of the present invention can also be prepared as follows.

건조된 곰보배추 및 상기 홍삼을 각각 세척 및 세절 후 건조된 재료 중량 대비 1 내지 20배, 바람직하게는, 약 4 내지 8 배 부피의 정제수를 포함한 물, 메탄올, 에탄올, 부탄올 등의 탄소수 1 내지 4의 저급알코올, 주정 또는 이들의 혼합용매로부터 선택된 용매, 바람직하게는 물 및 에탄올 혼합용매를 수회 섞은 다음에 30 내지 150℃, 바람직하게는 80 내지 120℃에서 1시간 내지 48시간, 바람직하게는 8시간 내지 14시간 동안 초음파 추출법, 열수 추출법, 상온 추출법 또는 환류추출법, 바람직하게는 환류 추출법을 약 1 내지 20회, 바람직하게는 2 내지 10회 반복 수행하는 제 1단계; 상기 1단계에서 얻은 추출액을 여과, 감압 농축, 및 건조하여 얻는 개개 추출물을 수득하는 제 2단계; 제 2단계의 개개 건조 추출물 분말을 건조 중량 상대 배합비가 1 : 0.01 내지 100(w/w)의 배합 중량부, 바람직하게는, 1 : 0.5 내지 50(w/w)의 배합 중량부, 보다 바람직하게는, 1: 0.1 내지 10(w/w)의 배합 중량부, 보다 더 바람직하게는 1: 0.3 내지 5 (w/w)의 배합 중량부, 가장 바람직하게는 1: 1 내지 3 (w/w)로 배합하여 제 3단계 공정을 통하여 본 발명의 조합 추출물을 얻을 수 있다.The dried pale green cabbage and the red ginseng are washed with water containing purified water having a volume of 1 to 20 times, preferably about 4 to 8 times the volume of the dried material after washing and fibrillation, respectively, water, methanol, ethanol, Of a lower alcohol, a solvent or a mixed solvent thereof, preferably water and an ethanol mixed solvent, and then stirring at 30 to 150 ° C, preferably 80 to 120 ° C, for 1 to 48 hours, preferably 8 1 to 20 times, preferably 2 to 10 times, by ultrasonic extraction, hot water extraction, room temperature extraction or reflux extraction, preferably reflux extraction, for a period of from 1 hour to 14 hours. A second step of obtaining an individual extract obtained by filtering, concentrating under reduced pressure, and drying the extract obtained in step 1; The individual dry extract powder of the second stage is mixed in a dry weight relative proportion of 1: 0.01 to 100 (w / w), preferably 1: 0.5 to 50 (w / w) (W / w), more preferably 1: 0.3 to 5 (w / w), most preferably 1: 1 to 3 (w / w), and the combined extract of the present invention can be obtained through a third step process.

본 발명의 추출물을 유효성분으로 함유하는 조성물은, 조성물 총 중량에 대하여 상기 추출물을 0.1 ~ 50 중량% 포함한다. The composition containing the extract of the present invention as an active ingredient contains 0.1 to 50% by weight of the above extract relative to the total weight of the composition.

상기한 제조방법으로 제조한 조합 추출물을 대상으로 본 발명에 따른 조합 추출물을 대상으로 활성산소종 발생 억제 평가 시험( 실험예 1)을 통하여 강력한 활성산소종 억제 효과를 나타냄을 확인하였으며, 류코트리엔 (leukotriene) 발생 억제능 평가( 실험예 2) 을 통하여 강력한 류코트리엔(leukotriene) 발생 억제 효과를 나타냄을 확인하였으며, 총 기관지폐포세척액 ( BAL ; bronchoalveolar lavage ) 세포수 측정실험 ( 실험예 3)을 통하여 강력한 총 BAL 세포수 감소 효과를 나타냄을 확인하였으며, 기관지폐포세척액(BAL fluid)내 백혈구( leukotcyte ) 중 CD11b +/ Gr -1+ 세포비율 측정( 실험예 4) 을 통하여 강력한 CD11b+/Gr-1+ leukocyte의 비율 억제 효과를 나타냄을 확인하였으며, 폐내 시토킨 ( cytokine ) mRNA 발현 수준에 미치는 영향실험 ( 실험예 5)을 통하여 강력한 염증성 사이토카인 및 염증인자 발현 수준 억제 효과를 나타냄을 확인하였으며, 기관지폐포세척액(BAL fluid)내 염증인자 발현 수준에 미치는 영향실험 ( 실험예 6)을 통하여 강력한 염증성 사이토카인 및 염증인자 발현 수준 억제 효과를 나타냄을 확인하였으며, 폐조직 변화에 미치는 영향실험 (실험 예 7)을 통하여 폐세포 벽이 얇아지고 교원섬유가 감소하는 것을 확인하였으며, 특히, 본원 발명의 조합 추출물을 투여시에 상승적인 기관지염증 억제 또는 치료효과를 나타냄을 확인함으로서 안전하면서 호흡기염증 질환에 대한 강력한 치료효능을 확인함으로서 호흡기염증 질환의 예방 또는 치료에 유용하게 사용될 수 있다. The method for manufacturing a combined extract of the active oxygen species generated by the target combined extracts according to the invention to target the inhibition evaluation test prepared in (Example 1) a strong active oxygen inhibitory effect was confirmed indicates via, leukotrienes (leukotriene) generated inhibitory ability evaluation (Test Example 2) through was confirmed strong leukotrienes (leukotriene) generated indicates an inhibitory effect, a total of BAL fluid (BAL the ; bronchoalveolar lavage ) Cell number measurement experiment ( Experimental example 3) it was found a strong total BAL cell count indicates the reduction through, bronchoalveolar lavage (BAL fluid) within the white blood cells (leukotcyte) of the CD11b + / Gr -1+ Powerful CD11b + / through the measuring cell ratio (Example 4) It has confirmed that the inhibitory effect refers to the ratio of Gr-1 + leukocyte, intrapulmonary Cytokine (cytokine) effects on mRNA expression level experiment (Experiment 5) showed strong inflammatory cytokine and inhibitory effects on inflammatory factor expression level. In bronchoalveolar lavage fluid (BAL fluid) Influence on Inflammatory Factor Expression Level ( Experimental Example 6) has confirmed that the strong inflammatory cytokines and inflammatory markers represent the expression level of inhibitory effect through, through the effect experiments on lung tissue changes (Example 7) The closed-cell wall thinning was confirmed that the decrease in collagen fibers, In particular, by confirming that synergistic bronchial inflammation is suppressed or therapeutic effect upon administration of the combination extract of the present invention, it can be safely used for the prevention or treatment of respiratory inflammatory diseases by confirming the powerful therapeutic effect on respiratory inflammatory diseases .

따라서, 본 발명은 상기 제조방법으로 수득된 곰보배추 및 홍삼으로 구성된 조합 추출물을 유효성분으로 함유하는 호흡기염증 질환의 예방 또는 치료용 약학조성물 및 건강기능식품을 제공한다.Accordingly, the present invention provides a pharmaceutical composition and a health functional food for preventing or treating respiratory inflammatory disease, which comprises, as an active ingredient, a combination extract composed of pale blue cabbage and red ginseng obtained by the above production method.

또한, 곰보배추 및 홍삼은 오랫동안 식용되거나 생약으로 사용되어 오던 약재로서 본 발명의 추출물 역시 독성 및 부작용 등의 문제가 없다. In addition, the Chinese cabbage and red ginseng have long been used as edible or herbal medicine, and the extract of the present invention has no toxicity and side effects.

본 발명의 약학 조성물은, 조성물 총 중량에 대하여 상기 추출물을 0.1 내지 50 중량 %로 포함한다. The pharmaceutical composition of the present invention contains 0.1 to 50% by weight of the above extract relative to the total weight of the composition.

본 발명의 추출물을 포함하는 약학조성물은, 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다.The pharmaceutical compositions comprising the extract of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the production of pharmaceutical compositions.

본 발명의 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록 시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다.Examples of carriers, excipients and diluents that can be included in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

본 발명의 추출물을 포함하는 조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽 및 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. The composition containing the extract of the present invention may be formulated in the form of powders, granules, tablets, capsules, oral preparations such as suspensions, emulsions, syrups and aerosols, external preparations, suppositories and sterilized injection solutions, Can be used.

상세하게는, 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제 및 캡슐제 등이 포함되며, 이러한 고형제제는 상기 화합물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트 (calcium carbonate), 수크로스 (sucrose), 락토오스 (lactose) 및 젤라틴 등을 섞어 조제될 수 있다. More specifically, when formulating the composition, it can be prepared using a diluent or an excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, and the like. Solid formulations for oral administration include tablets, pills, powders, granules and capsules, which may contain at least one excipient such as starch, calcium carbonate, sucrose, ), Lactose, gelatin and the like.

또한, 단순한 부형제 이외에 마그네슘 스테아레이트 및 탈크 같은 윤활제들도 사용될 수 있다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제 및 시럽제 등이 해당되는데, 흔히 사용되는 단순 희석제인 물 및 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제 및 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제 및 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리 에틸렌 글리콜 및 올리브 오일과 같은 식물성 기름 및 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔 (witepsol), 마크로골, 트윈 (tween) 61, 카카오지, 라우린지 및 글리 세로젤라틴 등이 사용될 수 있다.In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral use include suspensions, solutions, emulsions and syrups. In addition to water and liquid paraffin which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, fragrances and preservatives may be included. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol and vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As a suppository base, witepsol, macrogol, tween 61, cacao paper, laurin, and glycerol gelatin can be used.

본 발명의 추출물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나 바람직한 효과를 위해서, 본 발명의 추출물은 (0.0001~100) mg/kg으로, 바람직하게는 (0.001~100) mg/kg의 양을 일일 1회 내지 수회로 나누어 투여할 수 있다. 조성물에서 본 발명의 추출물은 전체 조성물 총 중량에 대하여 (0.0001~50) 중량%의 함량으로 배합될 수 있다.The preferred dosage of the extract of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the administration route and the period of time, but can be appropriately selected by those skilled in the art. However, for the desired effect, the extract of the present invention can be administered in an amount of (0.0001-100) mg / kg, preferably (0.001-100) mg / kg, once or several times a day. In the composition, the extract of the present invention may be formulated in an amount of (0.0001 to 50) wt% based on the total weight of the total composition.

본 발명의 약학 조성물은 쥐, 마우스, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 및 뇌혈관내 (intracere broventricular) 주사에 의해 투여될 수 있다. The pharmaceutical composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine and intracerebroventricular injections.

또한, 본 발명은 곰보배추 및 홍삼으로 구성된 조합 추출물을 유효성분으로 함유하는 호흡기염증 질환의 예방 및 개선용 건강기능 식품을 제공한다. The present invention also provides a health functional food for prevention and improvement of respiratory inflammatory diseases, which comprises, as an active ingredient, a combination extract composed of pungent Chinese cabbage and red ginseng.

본원에서 정의되는 "건강기능식품"은 건강기능식품에 관한 법률 제6727호에 따른 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및 가공한 식품을 의미하며, "기능성"이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건 용도에 유용한 효과를 얻을 목적으로 섭취하는 것을 의미한다.&Quot; Health functional food " as defined herein means food prepared and processed using raw materials or ingredients having functionality useful to the human body in accordance with Law No. 6727 on Health Functional Foods. &Quot; Functional " Structure and function of the nutrient to control or physiological effects, such as to obtain a beneficial effect for health is intended to eat.

본 발명의 건강기능식품은, 조성물 총 중량에 대하여 상기 추출물을 0.01 내지 95%, 바람직하게는 1 내지 80% 중량백분율로 포함한다.The health functional food of the present invention contains 0.01 to 95% by weight, preferably 1 to 80% by weight, of the extract, based on the total weight of the composition.

또한, 본 발명의 질환의 예방 또는 개선을 위한 목적으로 산제, 과립제, 정제, 캡슐제, 환제, 현탁액, 에멀젼, 시럽 등의 약학 투여형태 또는 티백제, 침출차, 건강 음료 등의 형태인 건강기능식품으로 제조 및 가공이 가능하다.For the purpose of preventing or ameliorating the disease of the present invention, for the purpose of preventing or ameliorating the disease, a pharmaceutical dosage form such as a powder, a granule, a tablet, a capsule, a pill, a suspension, an emulsion or a syrup, Can be manufactured and processed.

또한, 본 발명은 곰보배추 및 홍삼으로 구성된 조합 추출물을 유효성분으로 함유하는 호흡기염증 질환의 예방 및 개선용 건강보조식품 또는 식품첨가물을 제공한다.The present invention also provides a health supplement or a food additive for preventing or ameliorating respiratory inflammatory diseases, which comprises a combination extract comprising pale blue cabbage and red ginseng as an active ingredient.

또한 상기 건강기능식품은 식품첨가물을 추가로 포함할 수 있으며, "식품첨가물"로서의 적합여부는 다른 규정이 없는 한 식품의약품 안정청에 승인된 식품첨가물공전의 총칙 및 일반시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 판정한다. In addition, the health functional food may further include food additives, and the suitability of the food functional food as a " food additive " Standards and standards.

상기 "식품첨가물공전"에 수재된 품목으로 예를 들어, 케톤류, 글리신, 구연산칼륨, 니코틴산, 계피산 등의 화학적 합성품, 감색소, 감초추출물, 결정셀롤로오스, 구아검 등의 천연첨가물, L-글루타민산나트륨제제, 면류첨가알칼리제, 보존료제제, 타르색소제제 등의 혼합 제제류들을 들 수 있다.Examples of the products listed in the above-mentioned "food additives" include natural products such as ketones, chemical products such as glycine, potassium citrate, nicotinic acid and cinnamic acid, coloring matter, licorice extract, crystalline cellulose, guar gum, Sodium laurate, sodium glutamate preparation, noodles-added alkaline agent, preservative agent, tar pigment preparation and the like.

본 발명의 추출물이 포함된 기능성 식품으로는 빵, 떡류, 건과류, 캔디류, 초콜릿류, 츄잉껌, 쨈류와 같은 과자류 아이스크림류, 빙과류, 아이스크림 분말류와 같은 아이스크림 제품류 우유류, 저지방 우유류, 유당분해우유, 가공유류, 산양유, 발효유류, 버터유류, 농축유류, 유크림류, 버터유, 자연치즈, 가공치즈, 분유류, 유청류와 같은 유가공품류 식육가공품, 알가공품, 햄버거와 같은 식육제품류 어묵, 햄, 소세지, 베이컨 등의 어육가공품과 같은 어육제품류 라면류, 건면류, 생면류, 유탕면류, 호화건먼류, 개량숙면류, 냉동면류, 파스타류와 같은 면류 과실음료, 채소류음료, 탄산음료, 두유류, 요구르트 등의 유산균음료, 혼합음료와 같은 음료 간장, 된장, 고추장, 춘장, 청국장, 혼합장, 식초, 소스류, 토마토케첩, 카레, 드레싱과 같은 조미식품 마가린, 쇼트닝 및 피자를 들 수 있으나, 이에 제한되는 것은 아니다.Examples of the functional food containing the extract of the present invention include confectionery ice creams such as bread, rice cake, dried fruit, candy, chocolate, chewing gum and confectionery, ice cream products such as ice cream, ice cream powder, low fat milk, Processed products such as processed oil, goat milk, fermented oil, butter oil, concentrated oil, yogurt cream, butter oil, natural cheese, processed cheese, milk powder, milk products, meat products such as hamburger meat products, ham , Fish oil products such as sausages, bacon, etc. Fish products such as noodles, noodles, noodles, noodles, noodles, luxury noodles, improved noodles, noodles such as frozen noodles, pasta, vegetable beverages, Seasonings such as beverages such as soy sauce, miso, kochujang, chunchu, chonggukjang, mixed berries, vinegar, sauce, tomato ketchup, curry, dressing, Lean, shortening, and pizza.

본 발명의 건강 기능성 음료 조성물은 지시된 비율로 필수 성분으로서 상기 추출물을 함유하는 외에는 다른 성분에는 특별한 제한이 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, (예를 들어, 포도당, 과당 등); 디사카라이드, (예를 들어 말토스, 슈크로스 등); 및 폴리사카라이드, (예를 들어 덱스트린, 시클로덱스트린 등)과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진 등)) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 mL 당 일반적으로 약 (1~20) g, 바람직하게는 약 (5~12) g이다.The health functional beverage composition of the present invention has no particular limitation on the other ingredients other than the above-mentioned extract as an essential ingredient in the indicated ratio, and may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. Examples of the above-mentioned natural carbohydrates include monosaccharides (e.g., glucose, fructose, etc.); Disaccharide, (e.g., maltose, sucrose, etc.); And polysaccharides (for example, dextrin, cyclodextrin and the like), and sugar alcohols such as xylitol, sorbitol and erythritol. As natural flavors other than those described above, natural flavors (such as tau martin, stevia extract (e.g., rebaudioside A, glycyrrhizin)) and synthetic flavors (saccharin, aspartame, etc.) have. The ratio of the natural carbohydrate is generally about (1 to 20) g, preferably about (5 to 12) g per 100 mL of the composition of the present invention.

상기 외에 본 발명의 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 조성물들은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다. In addition to the above-mentioned composition, the composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and intermediates (cheese, chocolate etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like. In addition, the compositions of the present invention may contain flesh for the production of natural fruit juices and fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

또한, 본 발명의 추출물은 목적 질환의 예방 효과를 목적으로 식품 또는 음료에 첨가될 수 있다. 이 때, 식품 또는 음료 중의 상기 추출물의 양은 전체 식품 중량의 0.01 내지 15 중량%로 가할 수 있으며, 건강 음료 조성물은 100 mL를 기준으로 0.02 내지 5 g, 바람직하게는 0.3 내지 1 g의 비율로 가할 수 있다.In addition, the extract of the present invention can be added to food or beverage for the purpose of preventing the objective disease. At this time, the amount of the extract in the food or drink may be 0.01 to 15% by weight of the total food, and the health drink composition may be added in a proportion of 0.02 to 5 g, preferably 0.3 to 1 g, .

상기 건강기능식품을 제조하는 과정에서 음료를 포함한 식품에 첨가되는 본 발명에 따른 추출물은 필요에 따라 그 함량을 적절히 가감할 수 있다.The extract according to the present invention, which is added to foods containing beverages in the course of manufacturing the health functional food, can be appropriately added or decreased as needed.

본 발명에 따른 조합 추출물을 대상으로 활성산소종 발생 억제 평가 시험( 실험예 1)을 통하여 강력한 활성산소종 억제 효과를 나타냄을 확인하였으며, 류코트리엔 ( leukotriene ) 발생 억제능 평가( 실험예 2) 을 통하여 강력한 류코트리엔(leukotriene) 발생 억제 효과를 나타냄을 확인하였으며, 총 기관지폐포세척액 ( BAL ; bronchoalveolar lavage ) 세포수 측정실험 ( 실험예 3)을 통하여 강력한 총 BAL 세포수 감소 효과를 나타냄을 확인하였으며, 기관지폐포세척액(BAL fluid)내 백혈구( leukotcyte ) 중 CD11b +/ Gr -1+ 세포비율 측정(실험예 4) 을 통하여 강력한 CD11b+/Gr-1+ leukocyte의 비율 억제 효과를 나타냄을 확인하였으며, 폐내 시토 킨(cytokine) mRNA 발현 수준에 미치는 영향실험 ( 실험예 5)을 통하여 강력한 염증성 사이토카인 및 염증인자 발현 수준 억제 효과를 나타냄을 확인하였으며, 기관지 폐포세척액(BAL fluid)내 염증인자 발현 수준에 미치는 영향실험 ( 실험예 6)을 통하여 강력한 염증성 사이토카인 및 염증인자 발현 수준 억제 효과를 나타냄을 확인하였으며, 폐조직 변화에 미치는 영향실험 (실험 예 7)을 통하여 폐세포 벽이 얇아지고 교원섬유가 감소하는 것을 확인하였으며, 특히, 본원 발명의 조합 추출물을 투여시에 상승적인 기관지염증 억제 또는 치료효과를 나타냄을 확인함으로서 안전하면서 호흡기염증 질환에 대한 강력한 치료효능을 확인함으로서 호흡기염증 질환의 예방 또는 치료에 유용하게 사용될 수 있다. Inhibiting the active oxygen species generated by the target combined extracts according to the invention Test (Test Example 1) a strong active oxygen inhibitory effect was confirmed indicates via, leukotrienes (leukotriene) generated inhibitory ability evaluation (Test Example 2) through was confirmed strong leukotrienes (leukotriene) generated indicates an inhibitory effect, a total of BAL fluid (BAL the ; bronchoalveolar lavage ) Cell number measurement experiment ( Experimental example 3) it was found a strong total BAL cell count indicates the reduction through, bronchoalveolar lavage (BAL fluid) within the white blood cells (leukotcyte) of the CD11b + / Gr -1+ Powerful CD11b + / through the measuring cell ratio (Example 4) It has confirmed that the inhibitory effect refers to the ratio of Gr-1 + leukocyte, intrapulmonary Cytokine (cytokine) effects on mRNA expression level experiment (Experiment 5) showed strong inflammatory cytokine and inhibitory effects on inflammatory factor expression level. In bronchoalveolar lavage fluid (BAL fluid) Influence on Inflammatory Factor Expression Level ( Experimental Example 6) has confirmed that the strong inflammatory cytokines and inflammatory markers represent the expression level of inhibitory effect through, through the effect experiments on lung tissue changes (Example 7) The closed-cell wall thinning was confirmed that the decrease in collagen fibers, In particular, by confirming that synergistic bronchial inflammation is suppressed or therapeutic effect upon administration of the combination extract of the present invention, it can be safely used for the prevention or treatment of respiratory inflammatory diseases by confirming the powerful therapeutic effect on respiratory inflammatory diseases .

도 1은 폐조직의 조직병리학적 검사 실험 결과를 나타낸 도이다. FIG. 1 is a diagram showing the results of histopathological examination of lung tissue. FIG.

이하, 본 발명의 이해를 돕기 위하여 바람직한 실시예를 제시한다. 그러나 하기의 실시예는 본 발명을 더욱 쉽게 이해하기 위하여 제공되는 것일 뿐, 실시예에 의하여 본 발명의 내용이 한정되는 것은 아니다.Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following examples are provided to further understand the present invention, and the present invention is not limited by the examples.

참고예 1: Reference Example 1: 곰보배추 추출물의 제조Manufacture of mulberry Chinese cabbage extract

곰보배추(Salvia Plebera R. Br, 전남 부안산)를 물로 세척해 오염물질을 제거하고 완전히 건조시켰다. 이와 같이 준비된 곰보배추 1.5 kg의 15배인 22.5 L의 30% 주정을 가해 80±2 ℃에서 4 시간동안 1차 추출을 마친 후, 1 μm의 크기를 갖는 여과지로 여과시키는 과정을 2회 반복해 얻은 추출물을 52.5±2.5 ℃ 및 650±30 mmHg의 진공에서 농축시켰다. 85.0±2.0 ℃에서 1시간동안 살균과정을 거친후 55℃로 냉각시켰으며, 분무건조기 (KL-8, 서강엔지니어링(주), 입구온도 190±10 ℃, 출구온도 95±5 ℃)를 이용해 곰보배추 추출물을 제조하였다. Salvia cabbage ( Salvia Plebera R. Br, Ansan , Jeonnam Province ) was washed with water to remove contaminants and completely dried. The 22.5 L of 30% alcohol, which is 15 times the weight of the prepared pale blue cabbage of 1.5 kg, was subjected to the first extraction at 80 ± 2 ° C. for 4 hours, followed by filtration with filter paper having a size of 1 μm. The extracts were concentrated in vacuo at 52.5 ± 2.5 ° C and 650 ± 30 mmHg. (KL-8, Sogang Engineering Co., Ltd., entrance temperature: 190 ± 10 ℃, outlet temperature: 95 ± 5 ℃), which was sterilized at 85.0 ± 2.0 ℃ for 1 hour and cooled to 55 ℃. Chinese cabbage extract was prepared.

일정량의 곰보배추를 물로 세척해 오염물을 제거하고 완전히 건조시켰다. 건조된 곰보배추 중량비의 15배의 30% 주정을 가해 80±2 ℃에서 4시간, 총 2회 추출하였다. 추출액을 감압농축기에 투입하여 고형분 비가 40 %이상 되도록 농축한 후 분무건조기를 이용하여 건조시켜 곰보배추 30% 주정 추출물(458g, 이하 “SP30”이라 함),을 제조하였다.A certain amount of pungent Chinese cabbage was washed with water to remove contaminants and completely dried. The extracts were extracted twice at a temperature of 80 ± 2 ° C for 4 hours. The extract was put into a vacuum concentrator, concentrated to a solid content ratio of 40% or more, and dried using a spray dryer to prepare 458 g ( hereinafter referred to as " SP30 ") of pale blue cabbage extract.

참고예 2:Reference Example 2: 홍삼 추출물의 제조 Production of red ginseng extract

2-1. 홍삼의 제조2-1. Manufacture of red ginseng

계약재배를 통해 수매한 6년근 수삼의 (한국인삼공사, 10 kg) 이물질을 선별하여 제거하였다. 이물이 선별된 수삼을 흐르는 물로 예비세척 후 초음파 세척기 (Branson 5210, Branson)를 이용하여 30분간 세척하여 수삼에 잔류하고 있는 흙, 이물 등을 제거하였다. 세척이 완료된 수삼을 증숙기 (KMC-1221, 제오이텍)를 이용하여 80~100℃에서 90~110분간 증숙하고 60~65℃에서 9시간 건조기 (KMC-1202D3, 제이오텍)를 이용하여 건조하였다 (수분함량 45~55%). 1차 기계 건조된 인삼을 2차로 13~17일간 자연건조하여 홍삼 2.7 kg을 수득하였다 (이하, RG1이라함, 수분함량 14%).The 6 - year - old ginseng (Korean ginseng corporation, 10 kg) foreign substances purchased through contract cultivation was selected and removed. The foreign matter was preliminarily washed with running water and then washed with an ultrasonic washing machine (Branson 5210, Branson) for 30 minutes to remove soil and foreign matter remaining in the ginseng. The washed ginseng was steamed at 80 to 100 ° C for 90 to 110 minutes using a booster (KMC-1221, Zeoetec) and dried at 60 to 65 ° C for 9 hours using a dryer (KMC-1202D3, Joyotec) (Moisture content 45 ~ 55%). The primary machine dried ginseng was naturally dried for 13 ~ 17 days in the second time to obtain 2.7 kg of red ginseng (hereinafter referred to as RG1, moisture content 14%).

2-2. 홍삼 추출물의 제조2-2. Production of red ginseng extract

상기에서 얻은 6년근 홍삼 (P. ginseng C.A . Meyer, 근 75%, 미 25%, 한국인삼공사) 500 g을 원적외선건조기((주)한국에너지기술, HKD-LAB)를 이용하여 100~120 ℃에서 15~20 분간 건조 후 절각하였다. 건조된 홍삼에 4~8 배의 증류수를 가해 85 ℃에서 8~12 시간 추출하고 추출액을 여과하여 0~10 ℃로 냉각하였다. 잔사에 대해서는 4~8 배의 증류수를 가해 8~12 시간 추출을 1~4 회 추가로 실시하여 추출액을 여과 후 모두 합하여 0~10 ℃로 냉각하였다. 냉각이 완료된 추출액을 4 ℃에서 10~20 분 동안 5,000~8,000rpm 속도로 원심분리기((주)한일사이메드, SUPRA22K)를 이용하여 원심 분리하여 침전물을 제거하고 회전감압농축기를 이용하여 50~60℃에서 71 °Brix가 되도록 농축하였다. 최종적으로 농축액에 멸균된 증류수를 가해 15 °Brix로 희석 후 분무 건조하여 홍삼농축액분말 (230g 이하 “PGW”이라 함)을 수득하였다.500 g of the 6-year old red ginseng ( P. ginseng CA Meyer , 75%, US 25%, Korean ginseng Corp.) obtained above was heated at 100-120 ° C using a far-infrared ray dryer (Korea Energy Technology Co., HKD-LAB) For 15 ~ 20 minutes. Dried red ginseng was added with 4 to 8 times distilled water and extracted at 85 ° C for 8 to 12 hours. The extract was filtered and cooled to 0 to 10 ° C. For the residue, 4 ~ 8 times of distilled water was added and extraction for 8 to 12 hours was further performed 1 to 4 times. The extract was filtered and then cooled to 0 to 10 ° C. The cooled extract was centrifuged at 4 ° C for 10 to 20 minutes at a rate of 5,000 to 8,000 rpm using a centrifugal separator (Hanil Sai Med Co., Ltd., SUPRA22K) to remove precipitates. The filtrate was centrifuged at 50 to 60 RTI ID = 0.0 > 71 C < / RTI > Finally, sterilized distilled water was added to the concentrate, diluted to 15 ° Brix, spray dried, and red ginseng concentrate powder (230 g Hereinafter referred to as " PGW ").

실시예 1: Example 1: 다양한 조합비의 혼합 추출물 제조Manufacture of mixed extracts with various combination costs

1-1. 혼합 추출물 (1-1. Mixed extract ( 0.3:10.3: 1 ))

상기 곰보배추 추출물과 홍삼 추출물을 중량 기준으로 0.3:1 (곰보배추 추출물 : 홍삼 추출물)로 하는 것을 제외하고 상기 제조방법과 동일한 방법으로 추출하고 개개 추출물을 상기 배합비로 완전하게 혼합하여 혼합추출물(이하, “CB1”이라 함)을 제조하였다.The above extracts were extracted by the same method as described above except that the pale blueberry extract and red ginseng extract were used in a weight ratio of 0.3: 1 (ginseng Chinese cabbage extract: red ginseng extract), and the individual extracts were thoroughly mixed at the compounding ratio , &Quot; CB1 ").

1-2. 혼합 추출물 (1:1)1-2. Mixed extract (1: 1)

상기 곰보배추 추출물과 홍삼 추출물을 중량 기준으로 1:1 (곰보배추 추출물 : 홍삼 추출물)로 하는 것을 제외하고 상기 제조방법과 동일한 방법으로 추출하고 개개 추출물을 상기 배합비로 완전하게 혼합하여 혼합추출물(이하, “CB2”이라 함)을 제조하였다.The above extracts were extracted in the same manner as the preparation method except that the pale blueberry extract and the red ginseng extract were used as a weight ratio of 1: 1 (ginseng cabbage extract: red ginseng extract), and the individual extracts were thoroughly mixed at the compounding ratio, , &Quot; CB2 ").

1-3. 혼합 추출물 (2:1)1-3. Mixed extract (2: 1)

상기 곰보배추 추출물과 홍삼 추출물을 중량 기준으로 2:1 (곰보배추 추출물 : 홍삼 추출물)로 하는 것을 제외하고 상기 제조방법과 동일한 방법으로 추출하고 개개 추출물을 상기 배합비로 완전하게 혼합하여 혼합추출물(이하, “CB3”이라 함)을 제조하였다.The above extracts were extracted by the same method as described above except that the pale blueberry extract and the red ginseng extract were used as a weight ratio of 2: 1 (pale blueberry extract: red ginseng extract), and the individual extracts were thoroughly mixed at the compounding ratio , &Quot; CB3 ").

1-4. 혼합 추출물 (3:1)1-4. Mixed extract (3: 1)

상기 곰보배추 추출물과 홍삼 추출물을 중량 기준으로 3:1 (곰보배추 추출물 : 홍삼 추출물)로 하는 것을 제외하고 상기 제조방법과 동일한 방법으로 추출하고 개개 추출물을 상기 배합비로 완전하게 혼합하여 혼합추출물(이하, “CB4”이라 함)을 제조하였다.The above extracts were extracted by the same method as described above except that the pale blueberry extract and the red ginseng extract were used in a weight ratio of 3: 1 (pale blueberry extract: red ginseng extract), and the individual extracts were thoroughly mixed at the compounding ratio , &Quot; CB4 ").

1-5. 혼합 추출물 (4:1)1-5. Mixed extract (4: 1)

상기 곰보배추 추출물과 홍삼 추출물을 중량 기준으로 4:1 (곰보배추 추출물 : 홍삼 추출물)로 하는 것을 제외하고 상기 제조방법과 동일한 방법으로 추출하고 개개 추출물을 상기 배합비로 완전하게 혼합하여 혼합추출물(이하, “CB5”이라 함)을 제조하였다.The above extracts were extracted by the same method as described above except that the pale blueberry extract and red ginseng extract were used as a weight ratio of 4: 1 (ginseng Chinese cabbage extract: red ginseng extract), and the individual extracts were thoroughly mixed at the compounding ratio , &Quot; CB5 ").

1-One- 6. 혼합6. Mix 추출물 (5:1) The extract (5: 1)

상기 곰보배추 추출물과 홍삼 추출물을 중량 기준으로 5:1 (곰보배추 추출물 : 홍삼 추출물)로 하는 것을 제외하고 상기 제조방법과 동일한 방법으로 추출하고 개개 추출물을 상기 배합비로 완전하게 혼합하여 혼합추출물(이하, “CB6”이라 함)을 제조하였다.The above extracts were extracted in the same manner as in the preparation method except that the pale blueberry extract and red ginseng extract were used in a weight ratio of 5: 1 (ginseng cabbage extract: red ginseng extract), and the individual extracts were thoroughly mixed at the compounding ratio, , &Quot; CB6 ").

1-7. 혼합 추출물 (10:1)1-7. The mixed extract (10: 1)

상기 곰보배추 추출물과 홍삼 추출물을 중량 기준으로 10:1 (곰보배추 추출물 : 홍삼 추출물)로 하는 것을 제외하고 상기 제조방법과 동일한 방법으로 추출하고 개개 추출물을 상기 배합비로 완전하게 혼합하여 혼합추출물(이하, “CB7”이라 함)을 제조하였다.The above extracts were extracted by the same method as described above except that the pale blueberry extract and red ginseng extract were used in a weight ratio of 10: 1 (ginseng cabbage extract: red ginseng extract), and the individual extracts were thoroughly mixed at the compounding ratio, , &Quot; CB7 ").

실험예 1: 총 기관지폐포세척액 (BAL; bronchoalveolar lavage) 세포수 측정Experimental Example 1: Measurement of total number of bronchoalveolar lavage (BAL) cells

상기 실시예 시료의 총 기관지폐포세척액 ( BAL ; bronchoalveolar lavage ) 세포수에 미치는 영향을 확인하기 위하여 하기와 같이 문헌에 기재된 방법을 응용하여 실험하였다 (Schins et al., Toxicol Appl Pharmacol. 195(1), 1-11 (2004)과 Smith et al., Toxicol Sci, 93(2), 390-399 (2006)). Total BAL fluid of the embodiment sample (BAL; bronchoalveolar lavage) as follows to confirm the effect on the cells were tested by applying the methods described in the literature (Schins et al., Toxicol Appl Pharmacol . 195 (1), 1-11 (2004) and Smith et al., Toxicol Sci , 93 (2), 390-399 (2006)).

1-1. 실험 방법1-1. Experimental Method

Balb/c male mouse를 각 군당 6마리로 하여 정상군을 제외한 모든 군에 미세먼지의 구성성분인 0.25 mg/ml coal, 10 mg/ml fly ash, 0.25 mg/ml diesel exhaust particle (DEP) 혼합물에 Alum의 최종농도가 8%가 되도록 혼합하고, 이 미세먼지 혼합물을 실험동물의 기도 및 코에 Intra-Nazal-Trachea (INT) injection 방법을 이용하여 실험 시작 3일, 6일차에 50 μl씩 직접 주입하였다. 상기의 양성대조군, 참고예 1 내지 2 및 제조예 1 내지 5를 각 군에 200 mg/kg의 농도로 0.5% sodium carboxymethyl cellulose (CMC, 419273, Sigma-Aldrich) 용액으로 희석하여 매일 (10일) 경구 투여하였다. 실험 시작후 11일차에 부검을 진행하여 BAL fluid를 회수하였다.A total of 6 Balb / c male mice were injected into each group, except for the normal group, in which 0.25 mg / ml coal, 10 mg / ml fly ash and 0.25 mg / ml diesel exhaust particles (DEP) Alum was mixed to a final concentration of 8%, and the fine dust mixture was directly injected into the airways and nose of the experimental animals using Intra-Nazal-Trachea (INT) injection method on the 3rd and 6th day of the experiment, Respectively. The above positive control, Reference Examples 1 to 2 and Preparation Examples 1 to 5 were diluted with 0.5% sodium carboxymethyl cellulose (CMC, 419273, Sigma-Aldrich) solution at a concentration of 200 mg / Orally. The autopsy was carried out on the 11th day after the start of the experiment to recover the BAL fluid.

1-2. 실험 결과1-2. Experiment result

상기 시료들에 대한 총 기관지폐포세척액 (BAL; bronchoalveolar lavage) 세포수에 미치는 영향을 측정한 결과를 하기 표 1에 나타내었다. 총 BAL 세포수는 유발군에 비해 감소한 것을 보여 상기 시료들이 모두 염증 수치 감소에 기여하는 것을 확인하였으며, 더욱이 단일 추출물인 참고예 1 내지 2에 비해 조합 추출물인 실시예 1 내지 7에서 보다 낮은 총 BAL 세포수를 보여 조합 추출물이 현저히 높은 기관지 염증 억제활성을 가짐을 나타냈다.Table 1 shows the results of measuring the effect on the number of bronchoalveolar lavage (BAL) cells of the above samples. The number of total BAL cells was decreased compared to the induction group, and it was confirmed that all of the samples contributed to the reduction of the inflammation level. Further, compared with the single extracts of Reference Examples 1 and 2, The number of cells showed that the combination extract had a significantly higher bronchial inflammation inhibitory activity.

총 gun 기관지폐포세척액Bronchoalveolar lavage fluid ( ( BALBAL ; ; bronchoalveolarbronchoalveolar lavagelavage ) ) 세포수에On cell number 미치는 영향 실험 결과 Impact test results 구분division Total BAL cell
(×105 cells/ml)Total BAL cell
(X 10 < 5 > cells / ml) 억제율
(유발군 기준)Inhibition rate
(Based on inducible group) 정상군Normal group 32.3±6.1432.3 ± 6.14 유발군Trigger group 117.0±8.5117.0 ± 8.5 양성대조군Positive control group 68.3±4.3968.3 ± 4.39 42%42% 참고예 1 (곰보배추 단미제)Referential Example 1 (pale brown cabbage) 65.0±5.2465.0 + - 5.24 44%44% 실시예 1- 1 (0.3:1 복합제)Example 1- 1 (0.3: 1 combination) 47.5±5.3647.5 ± 5.36 59%59% 실시예 1- 2 (1:1 복합제)Example 1- 2 (1: 1 combination) 40.1±11.6340.1 ± 11.63 66%66% 실시예 1- 3 (2:1 복합제)Example 1- 3 (2: 1 combination) 37.8±2.1337.8 ± 2.13 68%68% 실시예 1- 4 (3:1 복합제)Example 1- 4 (3: 1 combination) 33.3±1.7533.3 ± 1.75 72%72% 실시예 1- 5 (4:1 복합제)Example 1- 5 (4: 1 combination) 44.1±3.2844.1 ± 3.28 62%62% 실시예 1- 6 (5:1 복합제)Examples 1-6 (5: 1 combination) 49.7±8.3049.7 ± 8.30 58%58% 실시예 1- 7 (10:1 복합제)Examples 1-7 (10: 1 combination) 54.8±7.2654.8 ± 7.26 53%53% 참고예 2 (홍삼 단미제)REFERENCE EXAMPLE 2 (red ginseng) 67.3±5.7467.3 ± 5.74 42%42%

실험예 2 기관지폐포세척액(BAL fluid)내 백혈구(leukotcyte) 중 CD11b+/Gr-1+ 세포비율 측정Experimental Example 2 Measurement of CD11b + / Gr-1 + cell ratio in leukocyte in bronchoalveolar lavage fluid (BAL fluid)

상기 실시예 시료의 기관지폐포세척액(BAL fluid)내 백혈구( leukotcyte ) 중 CD11b+/Gr-1+ 세포비율에 미치는 영향을 확인하기 위하여 하기와 같이 문헌에 기재된 방법을 응용하여 실험하였다 (Beutner EH., Bacteriological Reviews., 25(1):49-76, ((1961)).The embodiments of the samples of bronchoalveolar lavage (BAL fluid) within the white blood cells (leukotcyte) as follows to confirm the effect of the CD11b + / Gr-1 + cell ratio were tested by applying the methods described in the literature (Beutner EH, Bacteriological Reviews ., 25 (1): 49-76, ((1961)).

2-1. 실험 방법2-1. Experimental Method

상기 실험예 3의 방법과 동일하게 진행하였다. 회수한 기관지폐포세척액(BAL fluid)를 대상으로 형광표지가 결합된 CD11b 항체 (553310, BD Biosciences, San Jose, CA, USA)및 Gr-1 항체(553128, BD Biosciences, San Jose, CA, USA)를 이용해 특이적 형광항체염색법(specific fluorescence fluorescent antibody staining method)을 진행하였으며, FACS(Fluorescence-activated cell sorting, BD Biosciences, San Jose, CA, USA)법을 이용해 전체 백혈구( leukotcyte ) 중 CD11b+/Gr-1+ leukocyte의 비율을 측정하였다.The same procedure as in Experimental Example 3 was carried out. (553310, BD Biosciences, San Jose, CA, USA) and Gr-1 antibody (553128, BD Biosciences, San Jose, CA, USA) were used for the collection of the collected BAL fluids . (CD11b + / Gr- 1 ) in whole leukocytes using FACS (Fluorescence-activated cell sorting, BD Biosciences, San Jose, CA, USA) 1 + leukocyte ratio was measured.

2-2. 실험 결과2-2. Experiment result

상기 시료들의 기관지폐포세척액(BAL fluid)내 백혈구(leukotcyte) 중의 CD11b+/Gr-1+ leukocyte의 비율을 측정한 결과를 하기 표 2에 나타내었다. 이들 모두에서 유발군에 비해 CD11b+/Gr-1+ leukocyte의 비율이 감소한 것을 확인하였으며 더욱이 단일 추출물인 참고예 1 내지 2에 비해 조합 추출물인 실시예 1 내지 6에서 보다 낮은 CD11b+/Gr-1+ leukocyte 비율을 나타내 현저히 높은 기관지 염증 억제활성을 나타냄을 확인하였다.The results of the measurement of the ratio of CD11b + / Gr-1 + leukocyte in the leukocyte in the BAL fluid of the above samples are shown in Table 2 below. In all of these, it was confirmed that the ratio of CD11b + / Gr-1 + leukocyte was decreased compared to the induction group and that the ratio of CD11b + / Gr-1 + leukocyte was lower than that of the combination extracts of Examples 1 to 6 , Indicating a significantly higher bronchial inflammation inhibitory activity.

기관지폐포세척액(BAL fluid)내Within the bronchoalveolar lavage fluid (BAL fluid) 백혈구( leukocyte( leukotcyteleukotcyte ) 중 ) Of CD11bCD11b +/+ / GrGr -1+ 세포비율에 미치는 영향 실험 결과-1 + cell ratio 구분division % CD11b/Gr-1% CD11b / Gr-1 억제율(유발군 기준)Inhibition rate (inducing group standard) 정상군Normal group 7.1±0.27.1 ± 0.2 유발군Trigger group 51.2±3.651.2 ± 3.6 양성대조군Positive control group 33.0±6.533.0 ± 6.5 36%36% 참고예 1 (곰보배추 단미제)Referential Example 1 (pale brown cabbage) 35.3±3.235.3 ± 3.2 31%31% 실시예 1- 1 (0.3:1 복합제)Example 1- 1 (0.3: 1 combination) 29.7±1.529.7 ± 1.5 42%42% 실시예 1- 2 (1:1 복합제)Example 1- 2 (1: 1 combination) 25.1±4.625.1 ± 4.6 51%51% 실시예 1- 3 (2:1 복합제)Example 1- 3 (2: 1 combination) 21.3±2.721.3 ± 2.7 58%58% 실시예 1- 4 (3:1 복합제)Example 1- 4 (3: 1 combination) 19.1±3.619.1 ± 3.6 63%63% 실시예 1- 5 (4:1 복합제)Example 1- 5 (4: 1 combination) 24.9±1.624.9 ± 1.6 51%51% 실시예 1- 6 (5:1 복합제)Examples 1-6 (5: 1 combination) 28.4±2.528.4 ± 2.5 44%44% 실시예 1- 7 (10:1 복합제)Examples 1-7 (10: 1 combination) 32.0±3.632.0 ± 3.6 35%35% 참고예 2 (홍삼 단미제)REFERENCE EXAMPLE 2 (red ginseng) 40.8±1.640.8 ± 1.6 20%20%

실험예Experimental Example 3:  3: 폐내In the lung 염증인자Inflammatory factor mRNAmRNA 발현 수준 측정 Measurement of expression level

상기 실시예 시료의 폐내 염증인자 mRNA 발현 수준에 미치는 영향을 확인하기 위하여 하기와 같이 문헌에 기재된 방법을 응용하여 실험하였다 (Adelroth E., Can Respir J., 18A-21A, (1998)). Intrapulmonary of Example Sample Inflammatory factor (Adelroth E., Can Respir ., 18A-21A, (1998)). In order to confirm the effect on the mRNA expression level, the method described in the literature was applied as follows.

폐내 염증인자 mRNA 발현 능력을 측정하기 위해 RT-PCR(realtime quantitative polymerase chain reaction) 평가 시험을 수행하였다. Real-time quantitative polymerase chain reaction (RT-PCR) evaluation tests were performed to measure the expression ability of the inflammatory factor mRNA.

3-1. 실험 방법3-1. Experimental Method

(1) (One) 폐조직에서In lung tissue RNA  RNA 분리 회수Separation number

기관지폐포세척액 ( BAL fluid) 대신 폐조직을 회수하는 것을 제외하고 상기 실험예 3의 방법과 동일하게 진행하였다. 적출한 폐조직에 RNAzolB (Tel-Test, Friendswood, USA) 500 mL를 넣고 용해될 때까지 분쇄하였다. 이 혼합 부유액에 CHCl3 50 mL를 첨가한 후 15초간 다시 혼합하였다. 이를 얼음에 15분간 방치한 후 13,000 rpm에서 원심 분리하였다. 약 200 mL의 상층액을 회수하여 동량의 2-propanol(I9516, Sigma-Aldrich, USA)을 혼합 후 천천히 흔들고 얼음에서 15분간 방치하였다. 이를 다시 13,000 rpm에서 원심 분리한 후 80% 에탄올로 수세하고 3분간 진공에서 건조하여 RNA를 추출하였다. 추출한 RNA는 DEPC (diethyl pyrocarbonate, 750023, Thermo Scientific, Massachusetts, USA)를 처리한 20 mL의 증류수에 녹이고 75 ℃에서 불활성화시킨 후에 1차 가닥 상보 (first strand complementary DNA, cDNA) 합성에 사용하였다. Except that instead of recovering the lung bronchoalveolar lavage (BAL fluid) and was conducted in the same manner as in the method of Example 3. 500 mL of RNAzol B (Tel-Test, Friendswood, USA) was added to the extracted lung tissue and pulverized until dissolved. 50 mL of CHCl 3 was added to the mixed suspension and mixed again for 15 seconds. This was left on ice for 15 minutes and then centrifuged at 13,000 rpm. Approximately 200 mL of the supernatant was collected and mixed with an equal volume of 2-propanol (I9516, Sigma-Aldrich, USA), then shaken slowly and left on ice for 15 minutes. After centrifugation at 13,000 rpm, the cells were washed with 80% ethanol and dried in vacuum for 3 minutes to extract RNA. The extracted RNA was dissolved in 20 mL of deionized water treated with DEPC (diethyl pyrocarbonate, 750023, Thermo Scientific, Massachusetts, USA) and inactivated at 75 ° C before use in the synthesis of first strand complementary DNA (cDNA).

(2) cDNA 합성(2) cDNA synthesis

준비된 총(total) RNA 2 μg을 2U/tubeDNase I(AB0620, Thermo Scientific, Massachusetts, USA)을 넣어 37 ℃에서 30분간 반응한 후 75 ℃에서 10분동안 변성시키고, 이에 10 mM dNTPs mix(4030, TaKaRa, Shiga, Japan) 2.5 mL, random sequence hexanucleotides(N8080127, Thermo Scientific, Massachusetts, USA) 1 mL , RNase inhibitor(2313A, TaKaRa, Shiga, Japan) 1 mL, 100 mM DTT(4029, TaKaRa, Shiga, Japan) 1 mL, 5×RT buffer(M5313, Promega, Wisconsin-Madison, USA) 4.5 mL를 가한 후, M-MLV RT(M1701, Promega, Wisconsin-Madison, USA) 4.5 mL를 다시 가하고 DEPC 처리된 증류수로서 최종 부피가 20 mL가 되도록 하였다. 혼합액을 잘 섞은 뒤 2,000 rpm에서 5초간 원심침강시키고 37 ℃ heating block(Multi-blok heater, TRIPUNITHURA, USA)에서 60분 동안 반응시켜 cDNA를 합성한 다음, 95 ℃에서 5분 동안 방치하여 M-MLV RT를 불활성화시켜 합성된 cDNA를 PCR에 사용하였다.2 μg of the prepared total RNA was reacted at 37 ° C for 30 minutes with 2U / tube DNase I (AB0620, Thermo Scientific, Massachusetts, USA) and denatured at 75 ° C for 10 minutes. 10 mM dNTPs mix (4030, 1 mL of RNase inhibitor (2313A, TaKaRa, Shiga, Japan), 1 mL of 100 mM DTT (4029, TaKaRa, Shiga, Japan) and 1 mL of random sequence hexanucleotides (N8080127, Thermo Scientific, ) Was added 4.5 mL of 5 × RT buffer (M5313, Promega, Wisconsin-Madison, USA) and then 4.5 mL of M-MLV RT (M1701, Promega, Wisconsin-Madison, The final volume was adjusted to 20 mL. The mixture was mixed well, centrifuged at 2,000 rpm for 5 seconds, and incubated for 60 minutes in a heating block (Multi-block heater, TRIPUNITHURA, USA) at 37 ° C. After incubation at 95 ° C for 5 minutes, M- The synthesized cDNA was used for PCR by inactivating RT.

(3) PCR(3) PCR

합성한 cDNA를 문헌(Galli et al., Nat Immunol., 6(2):135-42, (2005))에 기재된 RT-PCR법을 응용하여 하기와 같이 진행하였다. The synthesized cDNA was subjected to the RT-PCR method described in the literature (Galli et al., Nat Immunol ., 6 (2): 135-42, (2005)) as follows.

Sper-Taqman PCR Master mix(4304437, Applied Biosystems, San Mateo, USA)를 사용하였고, 프라이머 (primer, 표 3 참조)의 최종농도가 200 nM이 되게 반응시켰다. RT-PCR의 조건으로는 전 변성화(pre-denaturation)은 50℃에서 2분, 94℃에서 10분, 그리고 40 cycles을 95℃에서 0.15분, 60℃에서 1분 수행하였다. 내부 기준물질(Internal standard)로 GAPDH(4352339E, Thermo Scientific, Massachusetts, USA)를 사용하였다.Sper-Taqman PCR Master mix (4304437, Applied Biosystems, San Mateo, USA) was used and reacted to a final concentration of 200 nM of the primer (see Table 3). The conditions for RT-PCR were pre-denaturation at 50 ° C for 2 min, 94 ° C for 10 min, and 40 cycles at 95 ° C for 0.15 min and 60 ° C for 1 min. GAPDH (4352339E, Thermo Scientific, Massachusetts, USA) was used as an internal standard.

RT-PCR법 사용 프라이머Using RT-PCR method primer Target geneTarget gene PrimerPrimer SequencesSequences Sequence I.D.Sequence I.D. MUC5ACMUC5AC ForwardForward 5'-AGAATATCTTTCAGGACCCCTGCT-3'5'-AGAATATCTTTCAGGACCCCTGCT-3 ' 1One Reverse Reverse 5'-ACACCAGTGCTGAGCATACTTTT-3'5'-ACACCAGTGCTGAGCATACTTTT-3 ' 22 CCR5CCR5 ForwardForward 5'-ATTCTCCACACCCTGTTTCG-3'5'-ATTCTCCACACCCTGTTTCG-3 ' 33 Reverse Reverse 5'-AAGGTGGTCAGGAGGAGGAC-3'5'-AAGGTGGTCAGGAGGAGGAC-3 ' 44 GAPDH-VICGAPDH-VIC ProbeProbe 5'-CATGTTCCAGTATGACTCCACTCACG-35'-CATGTTCCAGTATGACTCCACTCACG-3 55

3-2. 실험 결과3-2. Experiment result

하기 표 4에서 알 수 있는 바와 같이, 상기 시료 투여군들의 염증인자 (MUC5AC, CCR5)는 유발군에 비해 감소하였다. 더욱이 단일 추출물인 참고예 1 내지 2에 비해 조합 추출물인 실시예 1 내지 7에서 보다 높은 염증인자 억제율을 보여 탁월한 기관지 염증 억제활성을 나타냄을 확인하였다. As can be seen in Table 4 below, the inflammatory factors (MUC5AC, CCR5) of the sample administration groups were decreased as compared with the induction group. In addition, compared to the reference extracts 1 and 2 which are single extracts, the extracts of Examples 1 to 7, which are combination extracts, showed a higher inhibitory rate of inflammatory factors and thus showed excellent bronchial inflammation inhibitory activity.

폐내In the lung 염증인자Inflammatory factor mRNAmRNA 발현에 미치는 영향에 미치는 영향 실험 결과 Effect on the Expression 구분division MUC5ACMUC5AC CCR5CCR5 발현양Expression level 억제율
(유발군 기준)Inhibition rate
(Based on inducible group) 발현양Expression level 억제율
(유발군 기준)Inhibition rate
(Based on inducible group) 정상군Normal group 1.66±0.941.66 + - 0.94 0.76±0.190.76 + 0.19 유발군Trigger group 5.29±0.755.29 ± 0.75 8.8±1.598.8 ± 1.59 양성대조군Positive control group 3.15±1.163.15 ± 1.16 40%40% 5.22±0.975.22 ± 0.97 41%41% 참고예 1
(곰보배추 단미제)Reference Example 1
(Momoko cabbage short course) 2.92±0.842.92 ± 0.84 45%45% 4.99±1.954.99 ± 1.95 43%43% 실시예 1-1
(0.3:1 복합제)Example 1-1
(0.3: 1 combination) 2.62±0.312.62 0.31 50%50% 4.69±0.694.69 ± 0.69 47%47% 실시예 1-2
(1:1 복합제)Examples 1-2
(1: 1 combination) 2.46±1.202.46 ± 1.20 53%53% 4.20±0.714.20 0.71 52%52% 실시예 1-3
(2:1 복합제)Example 1-3
(2: 1 combination) 2.22±0.982.22 ± 0.98 58%58% 4.14±1.394.14 ± 1.39 53%53% 실시예 1-4
(3:1 복합제)Examples 1-4
(3: 1 combination) 1.81±0.721.81 + - 0.72 66%66% 3.36±0.903.36 ± 0.90 62%62% 실시예 1-5
(4:1 복합제)Examples 1-5
(4: 1 combination) 2.12±0.622.12 + - 0.62 60%60% 3.98±0.873.98 + 0.87 55%55% 실시예 1-6
(5:1 복합제)Examples 1-6
(5: 1 combination) 2.38±0.282.38 ± 0.28 55%55% 4.03±1.644.03 ± 1.64 54%54% 실시예 1- 7
(10:1 복합제)Examples 1-7
(10: 1 combination) 2.65±0.832.65 ± 0.83 50%50% 4.90±0.764.90 + 0.76 44%44% 참고예 2
(홍삼 단미제)Reference Example 2
(Red ginseng) 3.40±0.633.40 0.63 36%36% 7.93±1.657.93 ± 1.65 10%10%

실험예 4: 기관지폐포세척액(BAL fluid)내 염증인자 발현 측정EXPERIMENTAL EXAMPLE 4 Expression of Inflammatory Factor in BAL Fluid

상기 실시예 시료의 기관지폐포세척액(BAL fluid)내 염증인자 발현 수준에 미치는 영향을 확인하기 위하여 하기와 같이 문헌에 기재된 방법을 응용하여 실험하였다 (Brandt EB et al., J. Allergy Clin. Immunol., 132(5):1194-1204, (2013)).In the bronchial alveolar lavage fluid (BAL fluid) of the above- (Allergy Clin. Immunol., 132 (5): 1194-1204, (2013)) were used to confirm the effect on the inflammatory factor expression level ).

기관지폐포세척액(BAL fluid)내 IL-17A, TNF-α MIP2, 그리고 CXCL-1과 같은 염증인자 발현을 측정하기 위해 ELISA를 이용하여 평가 시험을 수행하였다. Evaluation studies were performed using ELISA to measure expression of inflammatory factors such as IL-17A, TNF-α MIP2, and CXCL-1 in bronchoalveolar lavage fluid (BAL fluid) .

4-1. 실험 과정4-1. Experimental course

상기 실험예 3의 방법과 동일하게 진행하였다. 기관지폐포세척액(BAL fluid)에서 IL-17A, TNF-α MIP2, 그리고 CXCL-1을 수준을 ELISA로 측정하였다. IL-17A 항체(M1700, R&D Systems, Minneapolis, USA), TNF-α 항체(MTA00B, R&D Systems, Minneapolis, USA) MIP2 항체(MM200, R&D Systems, Minneapolis, USA), 및 CXCL-1 항체(MKC00B, R&D Systems, Minneapolis, USA)를 완충용액 희석하여 미세 웰(micro well)에 코팅한 후에 4 ℃에서 16시간 배양하였다. 각 웰(well)을 3회 세척(washing) 완충용액으로 세척한 후에 10배 희석한 혈청을 100 μl씩 분주하였다. The same procedure as in Experimental Example 3 was carried out. Levels of IL-17A, TNF-α MIP2, and CXCL-1 in bronchoalveolar lavage fluid (BAL fluid) were measured by ELISA. (MM200, R & D Systems, Minneapolis, USA) and CXCL-1 antibody (MKC00B, R & D Systems, Minneapolis, USA) R & D Systems, Minneapolis, USA) was coated on a micro well and diluted for 16 hours at 4 < [deg.] ≫ C. Each well was washed three times with washing buffer, and then 100 μl of 10-fold diluted serum was added to each well.

1 시간 동안 실온에서 방치한 후 2회 세척하고 Avidin-HRP가 결합된 항체 (DY007, R&D Systems, Minneapolis, USA)를 100 μl를 처리하고 1 시간 실온에서 방치한 후 다시 세척하였다. TMB 기질(DY007, R&D Systems, Minneapolis, USA)을 100 μl씩 분주하고 암소에서 30 분간 방치한 후 50 μl의 stop 용액(DY007, R&D Systems, Minneapolis, USA)을 처리한 후 450 nm에서 흡광도를 측정하였다. (DY007, R & D Systems, Minneapolis, USA) was treated with 100 μl of Avidin-HRP-conjugated antibody and left at room temperature for 1 hour and then washed again. (DY007, R & D Systems, Minneapolis, USA) was treated with 100 μl of TMB substrate (DY007, R & D Systems, Minneapolis, USA) and incubated in a dark place for 30 minutes. Absorbance was measured at 450 nm Respectively.

4-2. 실험 결과4-2. Experiment result

하기 표 5에서 알 수 있는 바와 같이, 상기 시료 투여군들의 염증인자 (IL-17A, TNF-α, MIP2, CXCL-1)는 유발군에 비해 감소하였다. 더욱이 단일 추출물인 참고예 1 내지 2에 비해 조합 추출물인 실시예 1 내지 7에서 보다 낮은 IL-17A, MIP2, CXCL-1 그리고 실시예 1 내지 6에서 보다 낮은 TNF-α 발현을 나타내 현저히 높은 기관지 염증 억제활성을 나타냄을 확인하였다. As shown in the following Table 5, the inflammatory factors (IL-17A, TNF-alpha, MIP2, and CXCL-1) of the sample administration groups were decreased as compared with the induction group. In addition, lower IL-17A, MIP2, CXCL-1 and lower TNF-a expression than Examples 1 and 2, which are combination extracts, compared with the single extracts of Examples 1 and 2, and significantly higher bronchial inflammation Inhibitory activity.

기관지폐포세척액(BAL fluid)내Within the bronchoalveolar lavage fluid (BAL fluid) 염증인자Inflammatory factor 발현에 미치는 영향 실험 결과 Effects on expression 구분division 농도 (pg/ml) / 유발군 기준 억제율(%)Concentration (pg / ml) / induction group inhibition rate (%) IL-17AIL-17A TNF-αTNF-a MIP2MIP2 CXCL-1CXCL-1 정상군Normal group 4.4 4.4 45.6 45.6 70.7 70.7 95.8 95.8 유발군Trigger group 13.2 13.2 87.2 87.2 164.5 164.5 231.1 231.1 양성대조군Positive control group 7.8 / 41%7.8 / 41% 46.3 / 47%46.3 / 47% 107.1 / 35%107.1 / 35% 166.6 / 28%166.6 / 28% 참고예 1
(곰보배추 단미제)Reference Example 1
(Momoko cabbage short course) 7.9 / 40%7.9 / 40% 47.2 / 46%47.2 / 46% 97.1 / 41%97.1 / 41% 152.5 / 34%152.5 / 34% 실시예 1- 1
(0.3:1 복합제)Example 1-
(0.3: 1 combination) 7.8 / 41%7.8 / 41% 29.5 / 66%29.5 / 66% 77.8 / 53%77.8 / 53% 139.8 / 40%139.8 / 40% 실시예 1-2
(1:1 복합제)Examples 1-2
(1: 1 combination) 7.8 / 41%7.8 / 41% 30.0 / 66%30.0 / 66% 75.0 / 54%75.0 / 54% 138.6 / 40%138.6 / 40% 실시예 1- 3
(2:1 복합제)Examples 1- 3
(2: 1 combination) 7.5 / 43%7.5 / 43% 28.1 / 68%28.1 / 68% 72.9 / 56%72.9 / 56% 137.5 / 41%137.5 / 41% 실시예 1-4
(3:1 복합제)Examples 1-4
(3: 1 combination) 6.0 / 55%6.0 / 55% 20.3 / 77%20.3 / 77% 64.1 / 61%64.1 / 61% 130.1 / 44%130.1 / 44% 실시예 1-5
(4:1 복합제)Examples 1-5
(4: 1 combination) 7.1 / 46%7.1 / 46% 36.3 / 58%36.3 / 58% 79.1 / 52%79.1 / 52% 145.6 / 37%145.6 / 37% 실시예 1-6
(5:1 복합제)Examples 1-6
(5: 1 combination) 7.2 / 45%7.2 / 45% 46.6 / 47%46.6 / 47% 84.3 / 49%84.3 / 49% 150.9 / 35%150.9 / 35% 실시예 1- 7
(10:1 복합제)Examples 1-7
(10: 1 combination) 7.8 / 41%7.8 / 41% 46.0 / 47%46.0 / 47% 89.5 / 46%89.5 / 46% 150.4 / 35%150.4 / 35% 참고예 2
(홍삼 단미제)Reference Example 2
(Red ginseng) 9.6 / 27%9.6 / 27% 53.2 / 39%53.2 / 39% 104.4 / 37%104.4 / 37% 162.9 / 30%162.9 / 30%

실험예Experimental Example 5:  5: 폐조직Lung tissue 검사분석 Inspection analysis

상기 실시예 시료의 폐조직 변화에 미치는 영향을 확인하기 위하여 하기와 같이 기존 문헌에 기재된 방법을 응용하여 실험하였다.In order to confirm the effect on the lung tissue change of the above-mentioned sample, the method described in the existing literature was applied as described below.

폐조직을 분리해 조직병리학적 이상을 확인하기 위해 문헌에 기재된 방법을 응용하여 H&E 염색법과 M-T 염색법을 통해 폐세포 벽 및 교원섬유를 관찰하였다.(Nandedkar SD et al., Blood., 112(6):2529-2538, (2008)).In order to identify the histopathological abnormality of lung tissue, lung tissue wall and collagen fibers were observed through H & E staining and MT staining using the method described in literature (Nandedkar SD et al., Blood ., 112 (6 ): 2529-2538, (2008)).

5-1. 실험 과정5-1. Experimental course

기관지폐포세척액(BAL fluid)대신 폐조직을 적출하는 것을 제외하고 상기 실험예 3의 방법과 동일하게 진행하였다. 적출한 폐를 즉시 고정용액인 10% formaldehyde 용액 (F8775, Sigma-Aldrich, USA)에 고정한 후 세절하여 흐르는 물에 8 시간 수세한 다음, epoxy (A3183, Sigma-Aldrich, USA)에 포매하고, 이것을 마이크로톰 (microtome, Leica RM2265, Wetzlar, Germany)으로 절편을 만들어 표준방법에 의하여 Hematoxylin & Eosin, collagen deposition 염색인 Masson-Trichrome (HT10516, Sigma-Aldrich, USA)염색해 400×의 광학현미경 (Bright contrast Microscope, Tokyo, Japan)으로 관찰하였다.The procedure was the same as that of Experimental Example 3 except that the lung tissue was removed in place of the bronchoalveolar lavage fluid (BAL fluid) . The extracted lungs were immediately fixed in 10% formaldehyde solution (F8775, Sigma-Aldrich, USA) as a fixative solution, washed with running water for 8 hours, embedded in epoxy (A3183, Sigma-Aldrich, USA) The sections were stained with a microtome (Leica RM2265, Wetzlar, Germany) and stained with Hematoxylin & Eosin, collagen deposition, Masson-Trichrome (HT10516, Sigma-Aldrich, USA) , Tokyo, Japan).

5-2. 실험 결과5-2. Experiment result

도 1에 나타낸 바와 같이, 상기 호흡기 손상 유발군에서 보면 정상군에 비해 폐세포 벽이 두꺼워지고 교원섬유가 크게 증가한 것을 볼 수 있다. 하지만 실시예의 조합 추출물을 투여했던 군에서는 정상군 수준으로 폐세포 벽이 얇아지고 교원섬유가 감소하는 것을 확인하였다.As shown in FIG. 1, in the respiratory-injury-inducing group, the lung cell wall becomes thicker and the collagen fibers are greatly increased compared with the normal group. However, in the group to which the combination extract of the examples was administered, it was confirmed that the pulmonary cell wall became thinner and the collagen fiber decreased to the normal group level.

본 발명의 추출물을 포함하는 조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Formulation examples of the composition containing the extract of the present invention will be described, but the present invention is not intended to be limited thereto but is only specifically described.

제제예 1. 산제의 제조Preparation Example 1. Preparation of powder

CB1 추출물 ------------------------------------------ 20 mgCB1 extract ------------------------------------------ 20 mg

유당 ----------------------------------------------- 100 mgLactose ----------------------------------------------- 100 mg

탈크 ------------------------------------------------ 10 mgTalc ------------------------------------------------ 10 mg

상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.The above components are mixed and filled in airtight bags to prepare powders.

제제예 2. 정제의 제조Formulation Example 2. Preparation of tablets

CB2 추출물 ----------------------------------------- 10 mgCB2 Extract ----------------------------------------- 10 mg

옥수수전분 ----------------------------------------- 100 mgCorn starch ----------------------------------------- 100 mg

유당 ----------------------------------------------- 100 mgLactose ----------------------------------------------- 100 mg

스테아린산 마그네슘 ---------------------------------- 2 mgMagnesium stearate ---------------------------------- 2 mg

상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

제제예 3. 캡슐제의 제조Formulation Example 3. Preparation of capsules

CB3 추출물 ------------------------------------------ 10 mgCB3 extract ------------------------------------------ 10 mg

결정성 셀룰로오스 ------------------------------------- 3 mgCrystalline cellulose - 3 mg

락토오스 ------------------------------------------- 14.8 mgLactose ------------------------------------------- 14.8 mg

마그네슘 스테아레이트 ------------------------------- 0.2 mgMagnesium Stearate ------------------------------- 0.2 mg

통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충진하여 캡슐제를 제조한다.The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

제제예 4. 주사제의 제조Formulation Example 4. Preparation of injection

CM4 추출물 -------------------------------------- 10 mgCM4 Extract -------------------------------------- 10 mg

만니톨 -------------------------------------------- 180 mgMannitol -------------------------------------------- 180 mg

주사용 멸균 증류수 ------------------------------ 2974 mgSterile sterilized distilled water for injection ------------------------------ 2974 mg

Na2HPO412H2O 26 mgNa 2 HPO 4 12 H 2 O 26 mg

통상의 주사제의 제조방법에 따라 1 앰플당 (2) 상기의 성분 함량으로 제조한다.(2) The above components are prepared per ampoule according to the usual injection preparation method.

제제예 5. 액제의 제조Formulation Example 5. Preparation of a liquid preparation

CB5 화합물 ----------------------------------------- 10 mgCB5 Compound ----------------------------------------- 10 mg

이성화당 --------------------------------------------- 10 gIsolation Party --------------------------------------------- 10 g

만니톨 ------------------------------------------------ 5 gMannitol ------------------------------------------------ 5 g

정제수 ----------------------------------------------- 적량Purified water -----------------------------------------------

통상의 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 100 로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.Each component was added to purified water in accordance with the usual liquid preparation method and dissolved, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed and then purified water was added thereto to adjust the whole volume to 100. The solution was filled in a brown bottle and sterilized to prepare a liquid preparation do.

제제예 6. 건강 식품의 제조Formulation Example 6. Preparation of Healthy Foods

CB1 추출물 --------------------------------------- 1000 mgCB1 extract --------------------------------------- 1000 mg

비타민 혼합물 --------------------------------------- 적량Vitamin mixture ---------------------------------------

비타민 A 아세테이트 -------------------------------- 70 ugVitamin A Acetate -------------------------------- 70 ug

비타민 E ------------------------------------------ 1.0 mgVitamin E ------------------------------------------ 1.0 mg

비타민 B1 ---------------------------------------- 0.13 mgVitamin B1 ---------------------------------------- 0.13 mg

비타민 B2 ---------------------------------------- 0.15 mgVitamin B2 ---------------------------------------- 0.15 mg

비타민 B6 ----------------------------------------- 0.5 mgVitamin B6 ----------------------------------------- 0.5 mg

비타민 B12 ---------------------------------------- 0.2 ugVitamin B12 ---------------------------------------- 0.2 ug

비타민 C ------------------------------------------- 10 mgVitamin C ------------------------------------------- 10 mg

비오틴 --------------------------------------------- 10 ugBiotin --------------------------------------------- 10 ug

니코틴산아미드 ------------------------------------ 1.7 mgNicotinic acid amide 1.7 mg

엽산 ----------------------------------------------- 50 ugFolic acid ----------------------------------------------- 50 ug

판토텐산 칼슘 ------------------------------------- 0.5 mgCalcium pantothenate ------------------------------------- 0.5 mg

무기질 혼합물 --------------------------------------- 적량Inorganic mixture ---------------------------------------

황산제1철 ---------------------------------------- 1.75 mgFerrous sulfate ---------------------------------------- 1.75 mg

산화아연 ----------------------------------------- 0.82 mgZinc oxide ----------------------------------------- 0.82 mg

탄산마그네슘 ------------------------------------- 25.3 mgMagnesium carbonate ------------------------------------- 25.3 mg

제1인산칼륨 ---------------------------------------- 15 mgPotassium phosphate monohydrate 15 mg

제2인산칼슘 ---------------------------------------- 55 mgSecondary calcium phosphate ---------------------------------------- 55 mg

구연산칼륨 ----------------------------------------- 90 mgPotassium citrate ----------------------------------------- 90 mg

탄산칼슘 ------------------------------------------ 100 mgCalcium carbonate ------------------------------------------ 100 mg

염화마그네슘 ------------------------------------- 24.8 mgMagnesium chloride ------------------------------------- 24.8 mg

상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

제제예 7. 건강 음료의 제조Formulation Example 7. Preparation of health drink

CB6 추출물 --------------------------------------- 1000 mgCB6 extract --------------------------------------- 1000 mg

구연산 ------------------------------------------ 1000 mgCitric acid ------------------------------------------ 1000 mg

올리고당 ------------------------------------------ 100 gOligosaccharide ------------------------------------------ 100 g

매실농축액 ------------------------------------------ 2 gPlum concentrate ------------------------------------------ 2 g

타우린 ---------------------------------------------- 1 gTaurine ---------------------------------------------- 1 g

정제수를 가하여 ----------------------------- 전체 900 mlAdd purified water ----------------------------- Total 900 ml

통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간동안 85에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다.The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 for about 1 hour. The resulting solution was filtered and sterilized in two containers for sterilization, Used in the manufacture of health beverage compositions.

<110> KT G CORPORATION KOREA GINSENG CORP. <120> A composition comprising an extract of Salvia pleia, and red ginseng, as an active ingredient for preventing or treating respiratory inflammation disease <130> DIF/2017-04-0001/MR <160> 5 <170> KoPatentIn 3.0 <210> 1 <211> 24 <212> DNA <213> Mus musculus <400> 1 agaatatctt tcaggacccc tgct 24 <210> 2 <211> 23 <212> DNA <213> Mus musculus <400> 2 acaccagtgc tgagcatact ttt 23 <210> 3 <211> 20 <212> DNA <213> Mus musculus <400> 3 attctccaca ccctgtttcg 20 <210> 4 <211> 20 <212> DNA <213> Mus musculus <400> 4 aaggtggtca ggaggaggac 20 <210> 5 <211> 26 <212> DNA <213> Mus musculus <400> 5 catgttccag tatgactcca ctcacg 26 <110> KT G CORPORATION          KOREA GINSENG CORP. <120> A composition comprising an extract of Salvia pleia, and red          ginseng, as an active ingredient for or treating          respiratory inflammation disease <130> DIF / 2017-04-0001 / MR <160> 5 <170> KoPatentin 3.0 <210> 1 <211> 24 <212> DNA <213> Mus musculus <400> 1 agaatatctt tcaggacccc tgct 24 <210> 2 <211> 23 <212> DNA <213> Mus musculus <400> 2 acaccagtgc tgagcatact ttt 23 <210> 3 <211> 20 <212> DNA <213> Mus musculus <400> 3 attctccaca ccctgtttcg 20 <210> 4 <211> 20 <212> DNA <213> Mus musculus <400> 4 aaggtggtca ggaggaggac 20 <210> 5 <211> 26 <212> DNA <213> Mus musculus <400> 5 catgttccag tatgactcca ctcacg 26

Claims (9)

곰보배추 및 홍삼의 건조 중량 상대 배합비가 1 : 0.01 내지 100(w/w)의 배합 중량부로 배합된 조합 생약의 물, 주정, 메탄올, 에탄올, 부탄올 또는 이들의 혼합용매에 가용한 추출물을 유효성분으로 함유하는 비염, 중이염, 인후염, 편도염, 폐렴, 천식 및 만성 폐쇄성 폐질환으로 이루어지는 군으로부터 선택된 호흡기염증 질환의 예방 및 치료용 약학조성물.An extract of a combined herb medicine combined with a dry weight relative proportion of pearl cabbage and red gins in a mixing weight ratio of 1: 0.01 to 100 (w / w), water, alcohol, ethanol, butanol or a mixed solvent thereof, Wherein the composition is selected from the group consisting of rhinitis, otitis media, sore throat, tonsillitis, pneumonia, asthma and chronic obstructive pulmonary disease. 삭제delete 제 1항에 있어서,
상기 홍삼은 3 내지 8년근 고려인삼 (Panax ginseng), 화기삼 (Panax quinquefolia), 전칠삼 (삼칠, Panax notoginseng), 죽절삼 (Panax vietnamensis), 파낙스 엘레가티오르 (Panax elegatior), 파낙스 완지아누스 (Panax wangianus), 또는 파낙스 피핀라티푸스 (Panax bipinratifidus) 인삼을 10 내지 60℃에서 1 내지 24시간 동안, 1차로 자연건조시키는 제 1단계; 상기 자연 건조된 인삼을 세척하고 2차로 수분만 제거되도록 자연 건조시키는 제 2단계; 상기 건조된 인삼을 60 내지 120℃에서, 1 내지 48시간 동안 1차 증숙하는 제 3단계; 상기 1차 증숙된 인삼을 30 내지 80℃에서 1 내지 72시간 동안, 3차 건조시켜 수분함량 40 내지 70% 범위의 1차 건조물을 수득하는 제 4단계; 상기 1차 건조물을 공정을 통하여 10 내지 60℃에서 2일 내지 30일 동안 자연 건조시켜 수분함량 10 내지 20% 범위의 최종 홍삼 건조물을 수득하는 제 5단계 공정을 통하여 수득된 홍삼임을 특징으로 하는 약학 조성물.The method according to claim 1,
The red ginseng is from 3 to 8 years old roots of Ginseng (Panax ginseng), hwagisam (Panax quinquefolia), jeonchilsam (thirty-seven, Panax notoginseng , Panax vietnamensis , Panax elegatior , Panax wangianus ), or Panax papine latipus ( Panax bipinratifidus ) a first step of naturally drying ginseng at 10 to 60 DEG C for 1 to 24 hours; A second step of washing the naturally dried ginseng and naturally drying the ginseng to remove only water in the second step; A third step of firstly agitating the dried ginseng at 60 to 120 DEG C for 1 to 48 hours; Thirdly drying the firstly cooked ginseng at 30 to 80 DEG C for 1 to 72 hours to obtain a primary dry product having a moisture content in the range of 40 to 70%; Characterized in that the primary dried material is naturally dried at 10 to 60 ° C for 2 to 30 days through a process to obtain final dried red ginseng having a moisture content of 10 to 20% Composition. 삭제delete 삭제delete 곰보배추 및 홍삼의 건조 중량 상대 배합비가 1 : 0.01 내지 100(w/w)의 배합 중량부로 배합된 조합 생약의 물, 주정, 메탄올, 에탄올, 부탄올 또는 이들의 혼합용매에 가용한 추출물을 유효성분으로 함유하는 비염, 중이염, 인후염, 편도염, 폐렴, 천식 및 만성 폐쇄성 폐질환으로 이루어지는 군으로부터 선택된 호흡기염증 질환의 예방 또는 개선용 건강기능식품.An extract of a combined herb medicine combined with a dry weight relative proportion of pearl cabbage and red gins in a mixing weight ratio of 1: 0.01 to 100 (w / w), water, alcohol, ethanol, butanol or a mixed solvent thereof, Or a pharmaceutically acceptable salt thereof, for the prevention or amelioration of a respiratory inflammatory disease selected from the group consisting of rhinitis, otitis media, sore throat, tonsillitis, pneumonia, asthma and chronic obstructive pulmonary disease. 제 6항에 있어서,
상기 건강기능식품은 산제, 과립제, 정제, 캡슐제, 환제, 현탁액, 에멀젼, 시럽의 약학 투여형태 또는 티백제, 침출차, 건강 음료의 형태인 건강기능식품.The method according to claim 6,
The health functional food may be a pharmaceutical dosage form of a powder, a granule, a tablet, a capsule, a pill, a suspension, an emulsion or a syrup, or a health functional food in the form of a tea bag, an oil- 곰보배추 및 홍삼의 건조 중량 상대 배합비가 1 : 0.01 내지 100(w/w)의 배합 중량부로 배합된 조합 생약의 물, 주정, 메탄올, 에탄올, 부탄올 또는 이들의 혼합용매에 가용한 추출물을 유효성분으로 함유하는 비염, 중이염, 인후염, 편도염, 폐렴, 천식 및 만성 폐쇄성 폐질환으로 이루어지는 군으로부터 선택된 호흡기염증 질환의 예방 또는 개선용 건강보조식품.An extract of a combined herb medicine combined with a dry weight relative proportion of pearl cabbage and red gins in a mixing weight ratio of 1: 0.01 to 100 (w / w), water, alcohol, ethanol, butanol or a mixed solvent thereof, A dietary supplement for preventing or ameliorating a respiratory inflammatory disease selected from the group consisting of rhinitis, otitis media, sore throat, tonsillitis, pneumonia, asthma and chronic obstructive pulmonary disease. 삭제delete
KR1020170058865A 2017-05-11 2017-05-11 A composition comprising an extract of Salvia pleia, and red ginseng, as an active ingredient for preventing or treating respiratory inflammation disease KR101940042B1 (en)

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